Prediction of the clinicopathological subtypes of breast cancer using a Fisher discriminant analysis model based on radiomic features of diffusion-weighted MRI

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It is simplified and can be conducted easily in clinical practice, and this subtyping undoubtedly contributes to the treatment selection of breast cancer. This study aims to investigate the feasibility of using a Fisher discriminant analysis model based on radiomic features of diffusion-weighted MRI for predicting the clinicopathological subtypes of breast cancer. Methods: Patients who underwent breast magnetic resonance imaging were confirmed by retrieving data from our institutional picture archiving and communication system (PACS) between March 2013 and September 2017. Five clinicopathological subtypes were determined based on the status of ER, PR, HER2 and Ki-67 from the immunohistochemical test. The radiomic features of diffusion-weighted imaging were derived from the volume of interest (VOI) of each tumour. Fisher discriminant analysis was performed for clinicopathological subtyping by using a backward selection method. To evaluate the diagnostic performance of the radiomic features, ROC analyses were performed to differentiate between immunohistochemical biomarker-positive and -negative groups. Results: A total of 84 radiomic features of four statistical methods were included after preprocessing. The overall accuracy for predicting the clinicopathological subtypes was 96.4% by Fisher discriminant analysis, and the weighted accuracy was 96.6%. For predicting diverse clinicopathological subtypes, the prediction accuracies ranged from 92% to 100%. According to the cross-validation, the overall accuracy of the model was 82.1%, and the accuracies of the model for predicting the luminal A, luminal BHER2-, luminal BHER2+, HER2 positive and triple negative subtypes were 79%, 77%, 88%, 92% and 73%, respectively. According to the ROC analysis, the radiomic features had excellent performance in differentiating between different statuses of ER, PR, HER2 and Ki-67. Conclusions: The Fisher discriminant analysis model based on radiomic features of diffusion-weighted MRI is a reliable method for the prediction of clinicopathological breast cancer subtypes. Oncology Cancer Biology clinicopathological subtype Fisher discriminant analysis Diffusion-weighted imaging Figures Figure 1 Figure 2 Figure 3 Background Breast cancer is the second most common cancer cause of cancer death in females [1]. Based on gene expression profiling, four intrinsic molecular subtypes can be defined: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and basal-like [2-4]. One clinicopathological classification of breast cancer focused on therapeutic purposes has been adopted by the 12th International Breast Cancer Conference [5]. These clinicopathological subtypes are similar but not identical to the intrinsic molecular subtypes. There are five clinicopathological subtypes including luminal A, luminal B HER2- (luminal B/HER2 negative), luminal B HER2+ (luminal B/HER2 positive), HER2 positive and triple negative [5] (Table 1). Four immunohistochemical (IHC) biomarkers, including oestrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67, are recommended to define the clinicopathological subtypes. This classification is aimed at systematic therapy: luminal A cases require endocrine therapy; luminal B HER2- cases require endocrine therapy with or without cytotoxic therapy; luminal B HER2+ cases require cytotoxic, anti-HER2 and endocrine therapy; HER2 positive cases require cytotoxic and anti-HER2 therapy; and triple negative cases require cytotoxic therapy. At least two advantages of the clinicopathological subtypes are as follows: first, in contrast to high cost and time-consuming gene expression array testing, clinicopathological subtyping is simplified and can be conducted easily in clinical practice; second, this subtyping undoubtedly contributes to the treatment selection of breast cancer. Diffusion-weighted imaging (DWI) is an essential sequence that can monitor the mobility of water molecules. With restricted water diffusion, breast cancer usually shows hyperintensity on DW images [6]. DWI contributes to the differential diagnosis of breast lesions and may be a promising tool in breast cancer detection [7]. In differentiating malignant and benign breast lesions, the diagnostic performance of contrast-enhanced magnetic resonance imaging (MRI) with DWI is higher than that of contrast-enhanced MRI with time-intensity curves [8]. In addition, DWI also has the potential to monitor radiation-induced treatment response and neoadjuvant treatment response [9,10]. More importantly, DWI can be an alternative for breast cancer screening without contrast media [6]. Radiomics is a process of converting digital medical images into mineable high-dimensional data [11]. It has been used in the detection and diagnosis of cancer, assessment of prognosis, prediction of response to treatment, and monitoring of disease status [11,12]. The applications of radiomics in breast cancer include the prediction of molecular classification [13,14], assessment of tumour recurrence [15], and response to treatment [16]. Recently, radiomics, by using the image phenotyping of breast cancers and their surrounding parenchyma on dynamic contrast-enhanced MRI, was used to identify triple-negative breast cancer [13]. Another radiomic study showed a positive trend between the molecular cancer subtype and breast tumour phenotype of size and enhancement texture based on dynamic contrast-enhanced (DCE) MRI [14]. Unfortunately, the differential diagnosis of diverse molecular subtypes was not explored in this study. Mammographic radiomic features could also be used for the prediction of breast cancer molecular subtypes with oversimplified classifications such as triple-negative and non-triple-negative, HER2-enriched and non-HER2-enriched, and luminal and non-luminal [17]. Radiogenomics is a novel approach that can correlate imaging characteristics with underlying genes, mutations and expression patterns at the genetic level [18]. Radiogenomics can be imaging surrogates for genetic tests and can reflect tumour biology [19]. One recent study demonstrated that radiogenomics of breast cancer could infer underlying gene expression by using RNA sequencing [20]. Breast tumours with higher expression levels of the JAK/STAT and VEGF pathways had more intratumour heterogeneity in image enhancement texture detected by using dynamic contrast-enhanced MRI. Fan et al. showed that the image features of DCE-MRI were associated with gene expression modules and could predict the prognosis of breast cancer patients [21]. In addition, for breast cancer subtyping, the combination of correlated miRNAs and imaging features has better classification power in differentiating luminal A and other breast cancer subtypes than using miRNAs or imaging alone [22]. By means of deep learning or novel algorithms, the breast cancer molecular subtypes were differentiated based on image features from DCE-MRI [23,24]. As mentioned above, the clinicopathological subtypes of breast cancer are essential for treatment selection. Thus, it is urgent to develop a reliable method for the prediction of the clinicopathological subtypes. Diffusion-weighted imaging has high sensitivity in detecting breast cancer and is widely used in clinical practice. Herein, our study aims to verify the feasibility of using a radiomic approach based on DWI for the prediction of clinicopathological breast cancer subtypes. Methods Study population This retrospective study was approved by our institutional review board and the informed consent was waived. A total of 112 patients that underwent breast MRI were confirmed by retrieving data from our institutional picture archiving and communication system (PACS) between March 2013 and September 2017. The inclusion criteria were as follows: (1) patients who had suspected breast tumours and underwent breast MRI; (2) patients with malignant breast tumours confirmed by histopathological examination; (3) patients with ER, PR, HER2 and Ki-67 status obtained from immunohistochemical analysis; and (4) high-quality DW images used for outlining the lesions, without a size threshold for the lesions. The exclusion criteria were as follows: (1) patients with breast lesions who underwent any treatment before breast MRI, including surgery, chemotherapy, radiotherapy, or anti-HER2 therapy; (2) patients with bilateral breast lesions; (3) patients with suspected metastatic breast tumours; (4) DW images were illegible for assessment; (5) patients with pseudotumours or tumour-like lesions, including chronic inflammatory nodules, adenosis of the breast, and fat necrosis nodules; and (6) patients with tumours located in the skin and areola. Clinicopathological subtyping The immunohistochemical data of 112 patients were obtained by retrieval from the hospital information system. The statuses of ER, PR, HER2 and Ki-67 were determined by immunohistochemical tests. ER and PR expression were considered positive if at least 1% of tumour cells showed positive nuclear staining [25]. HER2 status was defined as positive if it presents an immunohistochemical score of 3+ and/or if in situ hybridization is positive [26]. A Ki-67 index higher than 14% is regarded as being at a high level [27]. There are five clinicopathological subtypes of breast cancers [5]: luminal A, ER and/or PR positive, HER2 negative and Ki-67 low (<14%); luminal B HER2- (luminal B/HER2 negative), ER and/or PR positive, HER2 negative and Ki-67 high; luminal B HER2+ (luminal B/HER2 positive), ER and/or PR positive, any Ki-67 and HER2 overexpressed or amplified; HER2 positive, HER2 overexpressed or amplified, ER and PR absent; triple negative, ER and PR absent, HER2 negative. Imaging data All 112 patients underwent breast MR examinations on a 3.0T MR system (MAGNETOM Skyra, Siemens Healthineers). Only diffusion-weighted MRI was used in this study. The DW imaging was performed with a 4-channel breast coil while the patients were in the prone position: axial imaging plane; repetition time/echo time, 5400/55 ms; field of view, 350 mm; voxel size, 1.8 × 1.8 × 5.0 mm; slice thickness 5 mm; spacing 0 mm; NEX 2; acquisition matrix 128 × 128; b value (s/mm 2 ), 0 and 800. The acquisition time of DWI was approximately 125 seconds. Other imaging protocols were as follows: (1) axial T2-weighted imaging with fat-suppression/SPAIR: repetition time/echo time, 3500/68 ms; field of view, 350 mm; voxel size, 0.5 × 0.5 × 5.0 mm; slice thickness 5 mm; flip angle 80°; NEX 1; (2) sagittal T2-weighted imaging with fat-suppression: repetition time/echo time, 3200/66 ms; field of view, 260 mm; voxel size, 0.8 × 0.8 × 4.0 mm; slice thickness 4 mm; flip angle 120°; NEX 1; (3) axial T1-weighted imaging without fat-suppression: repetition time/echo time, 6/2.46 ms; field of view, 340 mm; voxel size, 0.8 × 0.8 × 1.6 mm; slice thickness 1.6 mm; flip angle 15°; NEX 1; (4) 3D T1-weighted pre-contrast imaging with fat-suppression: repetition time/echo time, 4.49/1.68 ms; field of view, 340 mm; voxel size, 1.0 × 1.0 × 1.2 mm; slice thickness 1.2 mm; flip angle 10°; NEX 1; and (5) 3D-DCE T1-weighted imaging with fat-suppression by injection of Gd-DTPA (0.1 mmol/kg), acquiring seven phases after injection. The entire acquisition time was approximately 26 minutes. Image segmentation and feature extraction The diffusion-weighted images of each patient were saved and transferred to a radiomics analysis package, i.e., Artificial Intelligent Kit (A.K.) software (GE Healthcare, Shanghai, Version 3.0.1). The T2-weighted images and DCE-MR images were reviewed for lesion validation. The segmentation of breast tumours on DW images (b value, 800) was performed by using a two-step approach: first, the tumour margin was delineated manually slice by slice, and regions of interest (ROIs) were obtained; second, these ROIs were merged automatically by the A.K. software, and the volume of interest (VOI) of a tumour was finally completed. During ROI determination, both cystic and necrotic areas of the tumour were included in the ROI. Moreover, only the largest lesion was selected in patients with multiple unilateral tumours. A total of 396 radiomic features could be derived from the VOI of the DW image by A.K. software, as shown in Figure 1. These features were categorized into six statistical methods, including texture parameters, grey level size zone matrix (GLSZM), grey level co-occurrence matrix (GLCM), form factor parameters, run length matrix (RLM) and histogram. Texture parameters represent the appearance of the surface and how its elements are distributed. GLSZM provides a statistical representation by the estimation of a bivariate conditional probability density function of the image distribution values. GLCM represents the joint probability of certain sets of pixels with certain grey-level values. RLM is defined as the number of runs with pixels of grey-level i and run length j for a given direction θ. Pre-processing The training dataset was built by 396 radiomic parameters from 112 breast cancer cases. To eliminate redundant radiomic parameters, the pre-processing of the training dataset was performed as follows (Figure 2). First, if one value of a certain radiomic feature was out of the range of the mean ± standard deviation (SD), it would be considered an outlier and then removed from the dataset. Second, Pearson correlation analysis was conducted on two radiomic features in the training dataset, and if the correlation coefficient between pairwise features was above 0.9, one of the two features would be removed by random selection. Third, the mean centre and standard deviation scale were used to standardize the variables to the same value range. Finally, noise processing with linear smoothing filtering was automatically performed by A.K. software [28,29]. Classifier Building Fisher discriminant analysis was used for clinicopathological subtyping by using a backward selection method [30]. An approach of 104 iterations and 84 variables were used to establish the Fisher discriminant model (Function 1 to Function 5). To illustrate the process of building the Fisher discriminant model for the differential analysis of the five clinicopathological subtypes of breast cancer, the equations shown below were used, where X i was the radiomic feature used for the function building, and Y i was the class of one specified unbeknown patient. To ensure the accuracy of the model, we used the whole data set to calculate functions of Fisher discriminant model. Fisher discriminant model was trained by (n-1) samples and validated by the remaining sample. The leave-one-out cross-validation method was used for testing the Fisher discriminant analysis model. If the sample size was n , leave-one-out cross-validation was accomplished by the prediction of the remaining samples with the discriminant model established by n-1 samples, and the final prediction results for all samples would be obtained after the iterations ( n times) and then was regarded as the criteria standard for the prediction of the model [31]. To overcome the shortcoming of data imbalance, the mean class-weighted accuracy (CWA) was performed following the method proposed by Cohen et al [32]. The equation for k-class setting is as follow: Where w i is the weight assigned to class i and accu i is the accuracy rate computed over class i . Predicting different statuses of IHC biomarkers To predict the different statuses of immunohistochemical biomarkers, the diagnostic performance of radiomic features was assessed by receiver operating characteristic (ROC) curve analysis with a two-step approach. Radiomic features after pre-processing were included to calculate the predicted value of ER status, PR status, HER2 status and Ki-67 index by binary logistic regression. Then, ROC analysis was performed by using those predicted values. Based on the predicted values, ROC analyses were performed to differentiate between the ER positive and negative group, PR positive and negative group, HER2 positive and negative group, and Ki-67 low and high group. The comparison of the areas under two ROC curves was calculated by MedCalc software (Version 11.4.2, Mariakerke, Belgium) following the methodology of DeLong et al. [33]. Binary logistic regression and ROC analyses were performed using IBM SPSS software version 19.0 (IBM Corporation, New York). A p-value < 0.05 was considered statistically significant. Results There were 29 luminal A cases, 31 luminal B HER- cases, 17 luminal B HER+ cases, 24 HER2-positive cases and 11 triple-negative cases in our study (Table 2). A total of 162 radiomic features of four statistical methods were included after preprocessing. Of the 162 radiomic features, there were 42 histogram parameters, 18 texture parameters, 52 GLCM parameters and 50 RLM parameters. Each of 162 features would be evaluate in the Fisher discriminant analysis to determine its contribution, with which feature contributed to modelling would be held. Finally, 84 features were used for the model-building. The overall accuracy for predicting the clinicopathological subtypes was 96.4% by Fisher discriminant analysis. Based on class-weighted accuracy calculating, the overall weighted accuracy was 96.6%. For predicting diverse clinicopathological subtypes, the prediction accuracies ranged from 92% to 100%. When predicting subtypes of luminal B HER2- and triple negative, both accuracies were 100% (Table 3). A leave-one-out cross-validation was performed to test the Fisher discriminant analysis model. The overall accuracy of the model was 82.1% in the prediction of the clinicopathological subtypes of breast cancer. The accuracies of the model for predicting the luminal A, luminal B Her2- , luminal B Her2+ , Her2-positive and triple-negative subtypes were 79%, 77%, 88%, 92% and 73%, respectively (Table 3). The areas under the ROC curve (AUROCs) of histogram parameters, texture parameters, GLCM parameters and RLM parameters for predicting different IHC biomarkers are shown in detail in Table 4. Furthermore, the AUROCs of histogram parameters, GLCM parameters and RLM parameters were higher than those of texture parameters in assessing the status of ER, PR, HER2 and Ki-67 ( p < 0.001) (Table 5). Discussion Our study has shown that the Fisher discriminant analysis model with radiomic features of DW images can be used for predicting the clinicopathological subtypes of breast cancer. Furthermore, the model had excellent accuracies ranging from 92% to 100% in the prediction of clinicopathological subtypes. Based on the leave-one-out cross-validation, the overall accuracy was 82.1% when testing the Fisher discriminant analysis model. In our study, each clinicopathological subtype could be distinguished from others with high accuracy. Furthermore, we applied Fisher’s discriminant analysis to resolve a multiple classification problem, i.e., five clinicopathological subtypes of breast cancer. The clinicopathological subtypes of breast cancer are defined according to their therapeutic purposes. Our findings may contribute to decision-making and treatment selection in clinical practice, such as endocrine therapy, cytotoxic therapy, and anti-HER2 therapy [5]. As mentioned above, the molecular luminal B subtype is divided into two new clinicopathological subtypes, luminal B with or without HER2 overexpression (i.e., luminal B HER2- and luminal B HER2+ ). Luminal B HER2+ cases require cytotoxics, endocrine therapy and anti-HER2 therapy, whereas a luminal B HER2- cases does not require anti-HER2 therapy. Therefore, the clinicopathological subtype can provide detailed therapeutic information. Moreover, compared with molecular subtypes from gene assays, the clinicopathological subtypes from immunohistochemistry can be easily obtained with lower costs. In addition, leave-one-out cross-validation was performed to evaluate the accuracy of the Fisher discriminant analysis model. Our results showed that the overall accuracy of the model was 82.1% in predicting the clinicopathological subtypes. The accuracy for predicting HER2 positivity was up to 92%. We confirmed that the Fisher discriminant analysis model is a reliable method that can be used for predicting the clinicopathological subtypes of breast cancer. More importantly, our study validated the feasibility of using the Fisher discriminant analysis model to settle a multi-classification problem. In our study, we provided a noninvasive method for the prediction of the clinicopathological subtypes of breast cancer by using radiomic features of DWI. DWI is a widely used method that can measure the Brownian motion of water molecules. The motion of water molecules in tissue can be affected by tissue cellularity and membrane integrity [6]. DWI has been applied in the detection of breast cancer [34], differentiation of benign and malignant lesions [35], and monitoring the response to neoadjuvant chemotherapy [36,37]. However, there is no consensus that DWI is a reliable stand-alone method. One recent study showed that the combination of T2-weighted fat suppression and DWI textural features could predict sentinel lymph node metastasis [38]. By using diffusion MRI, a radiomic signature was shown to differentiate malignant from benign lesions [39]. Furthermore, another study showed that ADC values correlate with the biological features of breast cancer [40]. In addition to DWI mentioned above, a number of studies have focused on radiomic analysis from DCE-MRI. The imaging features from DCE-MRI can predict the luminal A and luminal B molecular subtypes [41] and can also differentiate between the histological and immunohistochemical subtypes of breast cancer [42]. One DCE-MRI feature that quantifies the relationship between lesion enhancement and background parenchymal enhancement is associated with the luminal B subtype of breast cancer [43]. However, these imaging feature-based studies provide insufficient information for the differential diagnosis of the five clinicopathological subtypes of breast cancer. To resolve this problem, our study focused on the prediction of clinicopathological subtypes by using DW imaging features and showed a high diagnostic performance with an overall accuracy of 96.4%. For predicting breast cancer receptor status and molecular subtyping, Leithner et al showed that the breast tumour segmentation approaches could affect the classification accuracy by using radiomic signature of DWI [44]. In their study, two segmentation approaches included: (1) segmentation ROI performed on high b value DWI and copied to ADC map; (2) segmentation ROI drawn directly on ADC map. The results indicated that tumour segmentation directly on ADC map was of better classification accuracy. However, in their study, some lesions could not be identified on ADC map. Our study only drawn segmentation ROI on DWI without ADC map, on which distinct tumour margin could easily be confirmed. The multiparametric MR radiomics using DCE and DWI can also be performed for predicting breast cancer subtypes [45]. Text features were extracted form DCE images of six contrast-enhanced phases and DWI with three b-values. The best accuracies of multiparametric MR radiomics model were 72.4% and 91.0% for the 4-IHC classification task and for the TN vs. non-TN cancers, respectively. However, for 4-IHC classification task, the accuracy of DWI with linear discriminant analysis model was 53.7% by using minor dependence emphasis on Kendall-tau-b. And for differentiating triple negative (TN) from non-TN tumours, the accuracy of DWI was 83.6% by using the maximum of variance. It indicated that the multiparametric MR radiomics performed well than DWI for 4-IHC classification task and for the TN vs. non-TN cancers. Recently, Leithner et al apply artificial intelligence (AI) to breast cancer molecular subtyping with multiparametric MR radiomics [46]. Texture features extracted from DCE images and ADC maps and a multi-layer perceptron feed-forward artificial neural network (MLP-ANN) were used for differentiation of TN and luminal A breast cancers from other subtypes. Their results indicated that multiparametric MR radiomics could provide prognostic and predictive information derived from the entire tumour before and during treatment. In predicting the different statuses of IHC biomarkers, excellent diagnostic performance of radiomic features was found in differentiating between the ER-positive and -negative group, PR-positive and -negative group, HER2-positive and -negative group, and Ki-67-low and -high group. However, there were relatively low AUROCs of texture parameters in assessing the status of these biomarkers. This result may be ascribed to a small number of 18 texture parameters. Compared with our results, one study using 38 radiomic features showed a less powerful result, with AUROCs ranging from 0.641 to 0.789 in predicting ER, PR and HER2 statuses [47]. Another study showed a similar result with AUROCs ranging from 0.65 to 0.89 [14]. Therefore, radiomics-based approach can serve as a non-invasive method for predicting breast cancer receptor status. In our study, histogram, GLCM and RLM features had high diagnostic performance in differentiating different IHC biomarkers. For differentiating ER-positive and ER-negative cases, PR-positive and PR-negative cases, HER2-positive and HER2-negative cases, and Ki-67-low and Ki-67-high cases, the AUROCs of histogram, GLCM and RLM features were 0.963-973, 0.923-0.939, 0.902-0.974 and 0.926-0.975, respectively. Furthermore, the Fisher discriminant analysis model had high accuracy in predicting the five clinicopathological subtypes of breast cancer. We concluded that radiomic features of DWI were highly associated with IHC biomarkers and could be emerging surrogates for IHC biomarkers. With the Fisher discriminant analysis model, we provided a new radiomic approach for breast cancer subtyping, and its findings contribute to treatment selection. Our study has some limitations. First, the main limitations of the study are its small sample size and lack of independent external validation, which makes the results difficult to reproduce in other populations. We will enlarge the sample size and apply other methods for the clinicopathological classification of breast cancer. Second, the automatic segmentation method was not applied in our study. Hence, the ROI delineation was time-consuming. Third, the apparent diffusion coefficient (ADC) value for each breast tumour was not acquired. Therefore, we failed to compare the diagnostic performance of ADC with that of radiomic features. Fourth, the lack of morphological features could limit our results. Our future work will focus on resolving these limitations. Conclusions Our study demonstrated that the Fisher discriminant analysis model based on radiomic features of diffusion-weighted MRI could be used for the prediction of the clinicopathological subtypes of breast cancer with high accuracy. Moreover, the radiomic features had excellent diagnostic performance in differentiating between the ER-positive and -negative groups, PR-positive and -negative groups, HER2-positive and -negative groups, and Ki-67-low and -high groups. More breast cancer cases will be enrolled in our future work to validate this radiomic approach. Abbreviations HER2: human epidermal growth factor receptor 2 IHC: immunohistochemical ER: oestrogen receptor PR: progesterone receptor DWI: diffusion-weighted imaging MRI: magnetic resonance imaging DCE-MRI: dynamic contrast-enhanced MRI PACS: picture archiving and communication system ROI: region of interest VOI: volume of interest GLSZM: grey level size zone matrix GLCM: grey level co-occurrence matrix RLM: run length matrix SD: standard deviation CWA: class-weighted accuracy ROC curve: receiver operating characteristic curve ADC: apparent diffusion coefficient Declarations 1. Ethics approval and consent to participate This retrospective study was approved by our institutional review board and the informed consent was waived. 2. Consent for publication Not applicable 3. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. 4. Competing interests The authors declare that they have no competing interests. 5. Funding: None 6. Authors' contributions: LZM: writing, methodology, formal analysis and interpretation. NM and ZXM: methodology and writing - original draft. LJ, GY and YH: writing - original draft. LZ and ZXX: writing - review and editing. All authors have read and approved the manuscript. 7. Acknowledgements: None References [1] American Cancer Society. Cancer Facts & Figures 2014. Atlanta: American Cancer Society; 2014. [2] Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–752. [3] Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumors. Nature. 2012;490(7418):61-70. [4] Huber KE, Carey LA, Wazer DE. Breast cancer molecular subtype in patients with locally advanced disease: impact on prognosis, pattern of recurrence, and response to therapy. Semin Radiat Oncol. 2009;19(4):204-210. 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[33] DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach.Biometrics. 1988 sep;44(3):837-45. [34] Sah RG, Agrwal K, Sharma U, et al. Characterization of malignant breast tissue of breast cancer patients and the normal breast tissue of healthy lactating women volunteers using diffusion MRI and in vivo 1H MR spectroscopy. J Magn Reson Imaging. 2015;41(1):169-174. [35] Cabuk G, Nass Duce M, Özgür A , et al. The diagnostic value of diffusion-weighted imaging and the apparent diffusion coefficient values in the differentiation of benign and malignant breast lesions. J Med Imaging Radiat Oncol. 2015;59(2):141-148. [36] Fujimoto H, Kazama T, Nagashima T, et al. Diffusion-weighted imaging reflects pathological therapeautic response and relapse in breast cancer. Breast Cancer. 2014;21(6):724-731. [37] Liu S, Ren R, Chen Z, et al. Diffusion-weighted imaging in assessing pathological response of tumor in breast cancer subtype to neoadjuvant chemotherapy. J Magn Reson Imaging. 2015;42(3):779-787. [38] Dong Y, Feng Q, Yang W, et al. Preoperative prediction of sentinel lymph node metastasis in breast cancer based on radiomics of T2-weighted fat-suppression and diffusion-weighted MRI. Eur Radiol. 2018;28(2):582-591. [39] Bickelhauht S, Paech D, Kickingereder P, et al. Prediction of malignancy by a radiomic signature from contrast agent-free diffusion MRI in suspicious breast lesions found on screening mammography. J Magn Reson Imaging. 2017;46(2):604-616. [40] Martincich L, Deantoni V, Bertotto I, et al. Correlations between diffusion-weighted imaging and breast cancer biomarkers. Eur Radiol. 2012;22(7):1519-1528. [41] Grimm LJ, Zhang J, Mazurowski MA. Computational approach to radiogenomics of breast cancer: Luminal A and luminal B molecular subtypes are associated with imaging features on routine breast MRI extracted using computer vision algorithms. J Magn Reson Imaging. 2015;42(4):902-907. [42] Waugh SA, Purdie CA, Jordan LB, et al. Magnetic resonance imaging texture analysis classification of primary breast cancer. Eur Radiol. 2016;26(2):322-330. [43] Mazuroski MA, Zhang J, Grimm LJ, et al. Radiogenomic analysis of breast cancer: luminal B molecular subtype is associated with enhancement dynamics at MR imaging. Radiology. 2014;273(2):365-372. [44] Leithner D, Bernard-Davila B, Martinez DF, et al. Radiomic Signatures Derived from Diffusion-Weighted Imaging for the Assessment of Breast Cancer Receptor Status and Molecular Subtypes. Mol Imaging Biol. 2020;22(2):453-461. [45] Xie T, Wang Z, Zhao Q, et al. Machine Learning-Based Analysis of MR Multiparametric Radiomics for the Subtype Classification of Breast Cancer. Front Oncol. 2019;9:505. [46] Leithner D, Mayerhoefer ME, Martinez DF, et al. Non-Invasive Assessment of Breast Cancer Molecular Subtypes with Multiparametric Magnetic Resonance Imaging Radiomics. J Clin Med. 2020;9(6):1853. [47] Guo W, Li H, Zhu Y, et al. Prediction of clinical phenotype in invasive breast carcinomas from the integration of radiomics and genomics data. J Med Imaging (Bellingham). 2015;2(4):041007. Tables Table 1. Clinicopathological Subtypes and Clinical Decision-Making Clinicopathological Subtype IHC status Clinical Decision-Making Luminal A ER and/or PR positive HER2 negative Ki-67 low (<14%) Endocrine therapy * Luminal B HER2- ER and/or PR positive HER2 negative Ki-67 high Endocrine±cytotoxic therapy & Luminal B HER2+ ER and/or PR positive any Ki-67 HER2 over-expressed Cytotoxics + anti-HER2 + endocrine therapy HER2 positive HER2 over-expressed Cytotoxics + anti-HER2 Triple negative ER and PR absent HER2 negative Cytotoxics *Luminal B HER2- , luminal B/HER2 negative; & Luminal B HER2+ , luminal B/HER2 positive; IHC, immunohistochemistry Table 2. General features and clinicopathological subtypes. Characteristic Patients (n=112) Clinicopathologic subtypes Luminal A Luminal B HER2- Luminal B HER2+ HER2 positive Triple negative Age 46.5(25~72) 46.1(25~69) 47.4(32~67) 44.6(26~69) 45.8(28~72) 49.5(30~61) ER status Positive 75 29 29 17 0 0 Negative 37 0 2 0 24 11 PR status Positive 69 27 29 13 0 0 Negative 43 2 2 4 24 11 HER2 status Positive 41 0 0 17 24 0 Negative 71 29 31 0 0 11 Ki-67 ≥ 14% 81 0 31 16 23 11 ＜ 14% 31 29 0 1 1 0 Table 3. Fisher discriminant analysis and cross-validation. Subtypes/n Training dataset Prediction accuracy 1 2 3 4 5 Fisher discriminant analysis 1 28 0 1 0 0 97% 2 0 31 0 0 0 100% 3 0 0 16 0 1 94% 4 1 1 0 22 0 92% 5 0 0 0 0 11 100% Total — — — — — — 96.4% Leave-one- out cross- validation 1 23 4 0 0 2 79% 2 1 24 0 1 5 77% 3 1 0 15 1 0 88% 4 0 2 0 22 0 92% 5 3 0 0 0 8 73% Total — — — — — — 82.1% Note: Subtypes: 1, luminal A; 2, luminal BHER2-; 3, luminal BHer2+; 4, HER2 positive; 5, triple negative. Table 4. ROC analysis of radiomic features in prediction of IHC status IHC status Radiomic feature AUROC ER(+) VS. ER(-) Histogram 0.973 (0.949-0.997) Texture 0.762 (0.674-0.851) GLCM 0.963 (0.929-0.998) RLM 0.967 (0.937-0.997) PR(+) VS. PR(­-) Histogram 0.925 (0.879-0.972) Texture 0.731 (0.637-0.824) GLCM 0.939 (0.892-0.986) RLM 0.923 (0.875-0.971) HER2(+) VS. HER2(-) Histogram 0.902 (0.847-0.957) Texture 0.722 (0.627-0.818) GLCM 0.911(0.860-0.962) RLM 0.974 (0.944-1.000) Ki-67 low VS. high Histogram 0.926 (0.870-0.981) Texture 0.718 (0.615-0.820) GLCM 0.975 (0.949-1.000) RLM 0.946 (0.905-0.988) Table 5. Comparison of ROC analysis results IHC status AUROC Z statistic p value ER(+) VS. ER(-) Histogram VS. Texture 4.531 <0.001 Histogram VS. GLCM 0.462 0.644 Histogram VS. RLM 0.312 0.7548 Texture VS. GLCM -4.147 <0.001 Texture VS. RLM -4.322 <0.001 GLCM VS. RLM -0.171 0.864 PR(+) VS. PR(­-) Histogram VS. Texture 3.676 <0.001 Histogram VS. GLCM -0.412 0.680 Histogram VS. RLM 0.058 0.954 Texture VS. GLCM -3.941 <0.001 Texture VS. RLM -3.607 <0.001 GLCM VS. RLM 0.462 0.644 HER2(+) VS. HER2(-) Histogram VS. Texture 3.189 0.001 Histogram VS. GLCM -0.236 0.814 Histogram VS. RLM -2.267 0.023 Texture VS. GLCM -3.407 <0.001 Texture VS. RLM -4.918 <0.001 GLCM VS. RLM -2.099 0.036 Ki-67 low VS. high Histogram VS. Texture 3.493 <0.001 Histogram VS. GLCM -1.542 0.123 Histogram VS. RLM -0.559 0.576 Texture VS. GLCM -4.795 <0.001 Texture VS. RLM -4.066 <0.001 GLCM VS. RLM 1.174 0.240 Supplementary Files Highlights.docx Cite Share Download PDF Status: Published Journal Publication published 09 Nov, 2020 Read the published version in BMC Cancer → Version 4 posted Submission checks completed at journal 20 Oct, 2020 Editorial decision: Accept 20 Oct, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4701","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":3716952,"identity":"08460175-c206-4619-a144-a3950aacbf63","order_by":0,"name":"Ming Ni","email":"","orcid":"","institution":"The affiliated hospital of qingdao university","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Ni","suffix":""},{"id":3716953,"identity":"a524b6d7-26a6-4789-b1f1-4ef204173e8b","order_by":1,"name":"Xiaoming Zhou","email":"","orcid":"","institution":"The affiliated hospital of qingdao university","correspondingAuthor":false,"prefix":"","firstName":"Xiaoming","middleName":"","lastName":"Zhou","suffix":""},{"id":3716954,"identity":"f5dcdd63-0f27-404d-97bd-0ad74f4ef1c6","order_by":2,"name":"Jingwei Liu","email":"","orcid":"","institution":"ShanDong University qilu hospital","correspondingAuthor":false,"prefix":"","firstName":"Jingwei","middleName":"","lastName":"Liu","suffix":""},{"id":3716955,"identity":"f859336a-c85d-4397-91b1-8577d569b8ff","order_by":3,"name":"Haiyang Yu","email":"","orcid":"","institution":"The affiliated hospital of qingdao university","correspondingAuthor":false,"prefix":"","firstName":"Haiyang","middleName":"","lastName":"Yu","suffix":""},{"id":3716956,"identity":"c06d4bf1-ccba-4dce-9efc-bc5f3b9645ed","order_by":4,"name":"Yuanxiang Gao","email":"","orcid":"","institution":"The affiliated hospital of qingdao university","correspondingAuthor":false,"prefix":"","firstName":"Yuanxiang","middleName":"","lastName":"Gao","suffix":""},{"id":3716957,"identity":"77a6ab07-9c7c-457b-a561-4b4a72b74f9e","order_by":5,"name":"Xuexi Zhang","email":"","orcid":"","institution":"GE Healthcare","correspondingAuthor":false,"prefix":"","firstName":"Xuexi","middleName":"","lastName":"Zhang","suffix":""},{"id":3716958,"identity":"7d666520-3fdd-40d4-ae9e-2cbb5974f34b","order_by":6,"name":"Zhiming Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIiWNgGAWjYDACCcYGhgQGBhkGBuYDQO4B4rXwMDCwJUC1MBPSAqGAWngMiNMiP7u5dcPDHbU8/Ow93yQ+1NxhMGfvx+86xjkH224knjnOI9lzdpvkjGPPGCx7DuO3hVkiEail7RiPwY3cbdI8bIcZDG4k49fCBtNif//NM+k//4Ba7j/Gr4UHoqWGx0CCh02asQ1kCwHvS0C0HOCROJNmbNnbd5jH4EyyAV4t8jPSn9382VYnx99++OGNH98OyxkcP/gAvzUQAA4kFlAc8RCjHATqQATzB2KVj4JRMApGwcgCAK1QTO+7EnhzAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-8248-7953","institution":"The affiliated hospital of Qingdao University","correspondingAuthor":true,"prefix":"","firstName":"Zhiming","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2019-09-02 14:59:31","currentVersionCode":4,"declarations":"","doi":"10.21203/rs.2.14001/v4","doiUrl":"https://doi.org/10.21203/rs.2.14001/v4","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12885-020-07557-y","type":"published","date":"2020-11-09T15:01:51+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":3207564,"identity":"2cdbc64e-839b-48d0-a24d-b4e0198eee75","added_by":"auto","created_at":"2020-10-26 21:19:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":270313,"visible":true,"origin":"","legend":"Workflow of Segmentation and Extraction of radiomic features","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4701/v4/14167e6659db5db3df13f59b.png"},{"id":3207566,"identity":"fd71ae9c-0de5-400c-b72e-2701ad437ee2","added_by":"auto","created_at":"2020-10-26 21:19:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":387725,"visible":true,"origin":"","legend":"Preprocessment of 396 radiomic features.","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4701/v4/f4445d481783ed22978d14e4.png"},{"id":3207567,"identity":"81a059f5-d7cf-4a3d-9f71-90386439c7e8","added_by":"auto","created_at":"2020-10-26 21:19:22","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":359148,"visible":true,"origin":"","legend":"ROC analysis of radiomic features. AUROCs of histogram parameters, GLCM parameters and RLM parameters were higher than those of texture parameters in assessing status of ER, PR, HER2 and Ki-67 (p \u003c 0.001).","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4701/v4/a69230a8ac234e8739ed9436.png"},{"id":13606295,"identity":"a3d14248-226d-4b10-8af5-8e7e57249fdd","added_by":"auto","created_at":"2021-09-17 06:07:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1273989,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4701/v4/ae006c1f-313d-47bf-b128-ebf5c582f83b.pdf"},{"id":3207565,"identity":"5da38671-1fb5-44d7-830d-c2738e58be43","added_by":"auto","created_at":"2020-10-26 21:19:22","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":13982,"visible":true,"origin":"","legend":"","description":"","filename":"Highlights.docx","url":"https://assets-eu.researchsquare.com/files/rs-4701/v4/8d0a7bd089da0d075c3b83b4.docx"}],"financialInterests":"","formattedTitle":"Prediction of the clinicopathological subtypes of breast cancer using a Fisher discriminant analysis model based on radiomic features of diffusion-weighted MRI","fulltext":[{"header":"Background","content":"\u003cp\u003eBreast cancer is the second most common cancer cause of cancer death in females [1]. Based on gene expression profiling, four intrinsic molecular subtypes can be defined: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and basal-like [2-4].\u003c/p\u003e\n\u003cp\u003eOne clinicopathological classification of breast cancer focused on therapeutic purposes has been adopted by the 12th International Breast Cancer Conference [5]. These clinicopathological subtypes are similar but not identical to the intrinsic molecular subtypes. There are five clinicopathological subtypes including luminal A, luminal B\u003csub\u003eHER2-\u003c/sub\u003e (luminal B/HER2 negative), luminal B\u003csub\u003eHER2+\u003c/sub\u003e (luminal B/HER2 positive), HER2 positive and triple negative [5] (Table 1). Four immunohistochemical (IHC) biomarkers, including oestrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67, are recommended to define the clinicopathological subtypes. This classification is aimed at systematic therapy: luminal A cases require endocrine therapy; luminal B\u003csub\u003eHER2-\u003c/sub\u003e cases require endocrine therapy with or without cytotoxic therapy; luminal B\u003csub\u003eHER2+ \u003c/sub\u003ecases require cytotoxic, anti-HER2 and endocrine therapy; HER2 positive cases require cytotoxic and anti-HER2 therapy; and triple negative cases require cytotoxic therapy. At least two advantages of the clinicopathological subtypes are as follows: first, in contrast to high cost and time-consuming gene expression array testing, clinicopathological subtyping is simplified and can be conducted easily in clinical practice; second, this subtyping undoubtedly contributes to the treatment selection of breast cancer.\u003c/p\u003e\n\u003cp\u003eDiffusion-weighted imaging (DWI) is an essential sequence that can monitor the mobility of water molecules. With restricted water diffusion, breast cancer usually shows hyperintensity on DW images [6]. DWI contributes to the differential diagnosis of breast lesions and may be a promising tool in breast cancer detection [7]. In differentiating malignant and benign breast lesions, the diagnostic performance of contrast-enhanced magnetic resonance imaging (MRI) with DWI is higher than that of contrast-enhanced MRI with time-intensity curves [8]. In addition, DWI also has the potential to monitor radiation-induced treatment response and neoadjuvant treatment response [9,10]. More importantly, DWI can be an alternative for breast cancer screening without contrast media [6].\u003c/p\u003e\n\u003cp\u003eRadiomics is a process of converting digital medical images into mineable high-dimensional data [11]. It has been used in the detection and diagnosis of cancer, assessment of prognosis, prediction of response to treatment, and monitoring of disease status [11,12]. The applications of radiomics in breast cancer include the prediction of molecular classification [13,14], assessment of tumour recurrence [15], and response to treatment [16]. Recently, radiomics, by using the image phenotyping of breast cancers and their surrounding parenchyma on dynamic contrast-enhanced MRI, was used to identify triple-negative breast cancer [13]. Another radiomic study showed a positive trend between the molecular cancer subtype and breast tumour phenotype of size and enhancement texture based on dynamic contrast-enhanced (DCE) MRI [14]. Unfortunately, the differential diagnosis of diverse molecular subtypes was not explored in this study. Mammographic radiomic features could also be used for the prediction of breast cancer molecular subtypes with oversimplified classifications such as triple-negative and non-triple-negative, HER2-enriched and non-HER2-enriched, and luminal and non-luminal [17]. Radiogenomics is a novel approach that can correlate imaging characteristics with underlying genes, mutations and expression patterns at the genetic level [18]. Radiogenomics can be imaging surrogates for genetic tests and can reflect tumour biology [19]. One recent study demonstrated that radiogenomics of breast cancer could infer underlying gene expression by using RNA sequencing [20]. Breast tumours with higher expression levels of the JAK/STAT and VEGF pathways had more intratumour heterogeneity in image enhancement texture detected by using dynamic contrast-enhanced MRI. Fan et al. showed that the image features of DCE-MRI were associated with gene expression modules and could predict the prognosis of breast cancer patients [21]. In addition, for breast cancer subtyping, the combination of correlated miRNAs and imaging features has better classification power in differentiating luminal A and other breast cancer subtypes than using miRNAs or imaging alone [22]. By means of deep learning or novel algorithms, the breast cancer molecular subtypes were differentiated based on image features from DCE-MRI [23,24].\u003c/p\u003e\n\u003cp\u003eAs mentioned above, the clinicopathological subtypes of breast cancer are essential for treatment selection. Thus, it is urgent to develop a reliable method for the prediction of the clinicopathological subtypes. Diffusion-weighted imaging has high sensitivity in detecting breast cancer and is widely used in clinical practice. Herein, our study aims to verify the feasibility of using a radiomic approach based on DWI for the prediction of clinicopathological breast cancer subtypes.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy population\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study was approved by our institutional review board and the informed consent was waived. A total of 112 patients that underwent breast MRI were confirmed by retrieving data from our institutional picture archiving and communication system (PACS) between March 2013 and September 2017. The inclusion criteria were as follows: (1) patients who had suspected breast tumours and underwent breast MRI; (2) patients with malignant breast tumours confirmed by histopathological examination; (3) patients with ER, PR, HER2 and Ki-67 status obtained from immunohistochemical analysis; and (4) high-quality DW images used for outlining the lesions, without a size threshold for the lesions. The exclusion criteria were as follows: (1) patients with breast lesions who underwent any treatment before breast MRI, including surgery, chemotherapy, radiotherapy, or anti-HER2 therapy; (2) patients with bilateral breast lesions; (3) patients with suspected metastatic breast tumours; (4) DW images were illegible for assessment; (5) patients with pseudotumours or tumour-like lesions, including chronic inflammatory nodules, adenosis of the breast, and fat necrosis nodules; and (6) patients with tumours located in the skin and areola.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinicopathological subtyping\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe immunohistochemical data of 112 patients were obtained by retrieval from the hospital information system. The statuses of ER, PR, HER2 and Ki-67 were determined by immunohistochemical tests. ER and PR expression were considered positive if at least 1% of tumour cells showed positive nuclear staining [25]. HER2 status was defined as positive if it presents an immunohistochemical score of 3+ and/or if in situ hybridization is positive [26]. A Ki-67 index higher than 14% is regarded as being at a high level [27]. There are five clinicopathological subtypes of breast cancers [5]: luminal A, ER and/or PR positive, HER2 negative and Ki-67 low (\u0026lt;14%); luminal B\u003csub\u003eHER2-\u003c/sub\u003e (luminal B/HER2 negative), ER and/or PR positive, HER2 negative and Ki-67 high; luminal B\u003csub\u003eHER2+\u003c/sub\u003e (luminal B/HER2 positive), ER and/or PR positive, any Ki-67 and HER2 overexpressed or amplified; HER2 positive, HER2 overexpressed or amplified, ER and PR absent; triple negative, ER and PR absent, HER2 negative.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eImaging data\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll 112 patients underwent breast MR examinations on a 3.0T MR system (MAGNETOM Skyra, Siemens Healthineers). Only diffusion-weighted MRI was used in this study. The DW imaging was performed with a 4-channel breast coil while the patients were in the prone position: axial imaging plane; repetition time/echo time, 5400/55 ms; field of view, 350 mm; voxel size, 1.8 \u0026times; 1.8 \u0026times; 5.0 mm; slice thickness 5 mm; spacing 0 mm; NEX 2; acquisition matrix 128 \u0026times; 128; b value (s/mm\u003csup\u003e2\u003c/sup\u003e), 0 and 800. The acquisition time of DWI was approximately 125 seconds. Other imaging protocols were as follows: (1) axial T2-weighted imaging with fat-suppression/SPAIR: repetition time/echo time, 3500/68 ms; field of view, 350 mm; voxel size, 0.5 \u0026times; 0.5 \u0026times; 5.0 mm; slice thickness 5 mm; flip angle 80\u0026deg;; NEX 1; (2) sagittal T2-weighted imaging with fat-suppression: repetition time/echo time, 3200/66 ms; field of view, 260 mm; voxel size, 0.8 \u0026times; 0.8 \u0026times; 4.0 mm; slice thickness 4 mm; flip angle 120\u0026deg;; NEX 1; (3) axial T1-weighted imaging without fat-suppression: repetition time/echo time, 6/2.46 ms; field of view, 340 mm; voxel size, 0.8 \u0026times; 0.8 \u0026times; 1.6 mm; slice thickness 1.6 mm; flip angle 15\u0026deg;; NEX 1; (4) 3D T1-weighted pre-contrast imaging with fat-suppression: repetition time/echo time, 4.49/1.68 ms; field of view, 340 mm; voxel size, 1.0 \u0026times; 1.0 \u0026times; 1.2 mm; slice thickness 1.2 mm; flip angle 10\u0026deg;; NEX 1; and (5) 3D-DCE T1-weighted imaging with fat-suppression by injection of Gd-DTPA (0.1 mmol/kg), acquiring seven phases after injection. The entire acquisition time was approximately 26 minutes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eImage segmentation and feature extraction\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe diffusion-weighted images of each patient were saved and transferred to a radiomics analysis package, i.e., Artificial Intelligent Kit (A.K.) software (GE Healthcare, Shanghai, Version 3.0.1). The T2-weighted images and DCE-MR images were reviewed for lesion validation. The segmentation of breast tumours on DW images (b value, 800) was performed by using a two-step approach: first, the tumour margin was delineated manually slice by slice, and regions of interest (ROIs) were obtained; second, these ROIs were merged automatically by the A.K. software, and the volume of interest (VOI) of a tumour was finally completed. During ROI determination, both cystic and necrotic areas of the tumour were included in the ROI. Moreover, only the largest lesion was selected in patients with multiple unilateral tumours.\u003c/p\u003e\n\u003cp\u003eA total of 396 radiomic features could be derived from the VOI of the DW image by A.K. software, as shown in Figure 1. These features were categorized into six statistical methods, including texture parameters, grey level size zone matrix (GLSZM), grey level co-occurrence matrix (GLCM), form factor parameters, run length matrix (RLM) and histogram. Texture parameters represent the appearance of the surface and how its elements are distributed. GLSZM provides a statistical representation by the estimation of a bivariate conditional probability density function of the image distribution values. GLCM represents the joint probability of certain sets of pixels with certain grey-level values. RLM is defined as the number of runs with pixels of grey-level \u003cem\u003ei\u003c/em\u003e and run length \u003cem\u003ej\u003c/em\u003e for a given direction \u0026theta;.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePre-processing\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe training dataset was built by 396 radiomic parameters from 112 breast cancer cases. To eliminate redundant radiomic parameters, the pre-processing of the training dataset was performed as follows (Figure 2). First, if one value of a certain radiomic feature was out of the range of the mean \u0026plusmn; standard deviation (SD), it would be considered an outlier and then removed from the dataset. Second, Pearson correlation analysis was conducted on two radiomic features in the training dataset, and if the correlation coefficient between pairwise features was above 0.9, one of the two features would be removed by random selection. Third, the mean centre and standard deviation scale were used to standardize the variables to the same value range. Finally, noise processing with linear smoothing filtering was automatically performed by A.K. software [28,29].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClassifier Building\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFisher discriminant analysis was used for clinicopathological subtyping by using a backward selection method [30]. An approach of 104 iterations and 84 variables were used to establish the Fisher discriminant model (Function 1 to Function 5).\u003c/p\u003e\n\u003cp\u003eTo illustrate the process of building the Fisher discriminant model for the differential analysis of the five clinicopathological subtypes of breast cancer, the equations shown below were used, where X\u003csub\u003ei\u003c/sub\u003e was the radiomic feature used for the function building, and Y\u003csub\u003ei\u003c/sub\u003e was the class of one specified unbeknown patient. To ensure the accuracy of the model, we used the whole data set to calculate functions of Fisher discriminant model. Fisher discriminant model was trained by (n-1) samples and validated by the remaining sample.\u003c/p\u003e\n\u003cp\u003e\u003cimg style=\"width: 402px;\" src=\"https://myfiles.space/user_files/44073_bbc9ffc5e562ebe7/44073_custom_files/img1602276266.png\" alt=\"\" /\u003e\u003c/p\u003e\n\u003cp\u003eThe leave-one-out cross-validation method was used for testing the Fisher discriminant analysis model. If the sample size was \u003cem\u003en\u003c/em\u003e, leave-one-out cross-validation was accomplished by the prediction of the remaining samples with the discriminant model established by \u003cem\u003en-1\u003c/em\u003e samples, and the final prediction results for all samples would be obtained after the iterations (\u003cem\u003en\u003c/em\u003e times) and then was regarded as the criteria standard for the prediction of the model [31].\u003c/p\u003e\n\u003cp\u003eTo overcome the shortcoming of data imbalance, the mean class-weighted accuracy (CWA) was performed following the method proposed by Cohen et al [32]. The equation for k-class setting is as follow:\u003c/p\u003e\n\u003cp\u003e\u003cimg style=\"width: 177px;\" src=\"https://myfiles.space/user_files/44073_bbc9ffc5e562ebe7/44073_custom_files/img1602276288.png\" alt=\"\" height=\"56\" /\u003e\u003c/p\u003e\n\u003cp\u003eWhere \u003cem\u003ew\u003csub\u003ei\u003c/sub\u003e\u003c/em\u003e is the weight assigned to class \u003cem\u003ei\u003c/em\u003e and \u003cem\u003eaccu\u003csub\u003ei\u003c/sub\u003e\u003c/em\u003e is the accuracy rate computed over class \u003cem\u003ei\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePredicting different statuses of IHC biomarkers\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo predict the different statuses of immunohistochemical biomarkers, the diagnostic performance of radiomic features was assessed by receiver operating characteristic (ROC) curve analysis with a two-step approach. Radiomic features after pre-processing were included to calculate the predicted value of ER status, PR status, HER2 status and Ki-67 index by binary logistic regression. Then, ROC analysis was performed by using those predicted values. Based on the predicted values, ROC analyses were performed to differentiate between the ER positive and negative group, PR positive and negative group, HER2 positive and negative group, and Ki-67 low and high group. The comparison of the areas under two ROC curves was calculated by MedCalc software (Version 11.4.2, Mariakerke, Belgium) following the methodology of DeLong et al. [33].\u003c/p\u003e\n\u003cp\u003eBinary logistic regression and ROC analyses were performed using IBM SPSS software version 19.0 (IBM Corporation, New York). A p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThere were 29 luminal A cases, 31 luminal B\u003csub\u003eHER-\u003c/sub\u003e cases, 17 luminal B\u003csub\u003eHER+\u003c/sub\u003e cases, 24 HER2-positive cases and 11 triple-negative cases in our study (Table 2).\u003c/p\u003e\n\u003cp\u003eA total of 162 radiomic features of four statistical methods were included after preprocessing. Of the 162 radiomic features, there were 42 histogram parameters, 18 texture parameters, 52 GLCM parameters and 50 RLM parameters. Each of 162 features would be evaluate in the Fisher discriminant analysis to determine its contribution, with which feature contributed to modelling would be held. Finally, 84 features were used for the model-building.\u003c/p\u003e\n\u003cp\u003eThe overall accuracy for predicting the clinicopathological subtypes was 96.4% by Fisher discriminant analysis. Based on class-weighted accuracy calculating, the overall weighted accuracy was 96.6%. For predicting diverse clinicopathological subtypes, the prediction accuracies ranged from 92% to 100%. When predicting subtypes of luminal B\u003csub\u003eHER2-\u003c/sub\u003e and triple negative, both accuracies were 100% (Table 3).\u003c/p\u003e\n\u003cp\u003eA leave-one-out cross-validation was performed to test the Fisher discriminant analysis model. The overall accuracy of the model was 82.1% in the prediction of the clinicopathological subtypes of breast cancer. The accuracies of the model for predicting the luminal A, luminal B\u003csub\u003eHer2-\u003c/sub\u003e, luminal B\u003csub\u003eHer2+\u003c/sub\u003e, Her2-positive and triple-negative subtypes were 79%, 77%, 88%, 92% and 73%, respectively (Table 3).\u003c/p\u003e\n\u003cp\u003eThe areas under the ROC curve (AUROCs) of histogram parameters, texture parameters, GLCM parameters and RLM parameters for predicting different IHC biomarkers are shown in detail in Table 4. Furthermore, the AUROCs of histogram parameters, GLCM parameters and RLM parameters were higher than those of texture parameters in assessing the status of ER, PR, HER2 and Ki-67 (\u003cem\u003ep \u003c/em\u003e\u0026lt; 0.001) (Table 5).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study has shown that the Fisher discriminant analysis model with radiomic features of DW images can be used for predicting the clinicopathological subtypes of breast cancer. Furthermore, the model had excellent accuracies ranging from 92% to 100% in the prediction of clinicopathological subtypes. Based on the leave-one-out cross-validation, the overall accuracy was 82.1% when testing the Fisher discriminant analysis model.\u003c/p\u003e\n\u003cp\u003eIn our study, each clinicopathological subtype could be distinguished from others with high accuracy. Furthermore, we applied Fisher\u0026rsquo;s discriminant analysis to resolve a multiple classification problem, i.e., five clinicopathological subtypes of breast cancer. The clinicopathological subtypes of breast cancer are defined according to their therapeutic purposes. Our findings may contribute to decision-making and treatment selection in clinical practice, such as endocrine therapy, cytotoxic therapy, and anti-HER2 therapy [5]. As mentioned above, the molecular luminal B subtype is divided into two new clinicopathological subtypes, luminal B with or without HER2 overexpression (i.e., luminal B\u003csub\u003eHER2-\u003c/sub\u003e and luminal B\u003csub\u003eHER2+\u003c/sub\u003e). Luminal B\u003csub\u003eHER2+\u003c/sub\u003e cases require cytotoxics, endocrine therapy and anti-HER2 therapy, whereas a luminal B\u003csub\u003eHER2-\u003c/sub\u003e cases does not require anti-HER2 therapy. Therefore, the clinicopathological subtype can provide detailed therapeutic information. Moreover, compared with molecular subtypes from gene assays, the clinicopathological subtypes from immunohistochemistry can be easily obtained with lower costs.\u003c/p\u003e\n\u003cp\u003eIn addition, leave-one-out cross-validation was performed to evaluate the accuracy of the Fisher discriminant analysis model. Our results showed that the overall accuracy of the model was 82.1% in predicting the clinicopathological subtypes. The accuracy for predicting HER2 positivity was up to 92%. We confirmed that the Fisher discriminant analysis model is a reliable method that can be used for predicting the clinicopathological subtypes of breast cancer. More importantly, our study validated the feasibility of using the Fisher discriminant analysis model to settle a multi-classification problem.\u003c/p\u003e\n\u003cp\u003eIn our study, we provided a noninvasive method for the prediction of the clinicopathological subtypes of breast cancer by using radiomic features of DWI. DWI is a widely used method that can measure the Brownian motion of water molecules. The motion of water molecules in tissue can be affected by tissue cellularity and membrane integrity [6]. DWI has been applied in the detection of breast cancer [34], differentiation of benign and malignant lesions [35], and monitoring the response to neoadjuvant chemotherapy [36,37]. However, there is no consensus that DWI is a reliable stand-alone method. One recent study showed that the combination of T2-weighted fat suppression and\u0026nbsp;DWI\u0026nbsp;textural features could predict sentinel lymph node metastasis [38]. By using diffusion MRI, a radiomic signature was shown to differentiate malignant from benign lesions [39]. Furthermore, another study showed that ADC values correlate with the biological features of breast cancer [40]. In addition to DWI mentioned above, a number of studies have focused on radiomic analysis from DCE-MRI. The imaging features from DCE-MRI can predict the luminal A and luminal B molecular subtypes [41] and can also differentiate between the histological and immunohistochemical subtypes of breast cancer [42]. One DCE-MRI feature that quantifies the relationship between lesion enhancement and background parenchymal enhancement is associated with the luminal B subtype of breast cancer [43]. However, these imaging feature-based studies provide insufficient information for the differential diagnosis of the five clinicopathological subtypes of breast cancer. To resolve this problem, our study focused on the prediction of clinicopathological subtypes by using DW imaging features and showed a high diagnostic performance with an overall accuracy of 96.4%.\u003c/p\u003e\n\u003cp\u003eFor predicting breast cancer receptor status and molecular subtyping, Leithner et al showed that the breast tumour segmentation approaches could affect the classification accuracy by using radiomic signature of DWI [44]. In their study, two segmentation approaches included: (1) segmentation ROI performed on high b value DWI and copied to ADC map; (2) segmentation ROI drawn directly on ADC map. The results indicated that tumour segmentation directly on ADC map was of better classification accuracy. However, in their study, some lesions could not be identified on ADC map. Our study only drawn segmentation ROI on DWI without ADC map, on which distinct tumour margin could easily be confirmed.\u003c/p\u003e\n\u003cp\u003eThe multiparametric MR radiomics using DCE and DWI can also be performed for predicting breast cancer subtypes [45]. Text features were extracted form DCE images of six contrast-enhanced phases and DWI with three b-values. The best accuracies of multiparametric MR radiomics model were 72.4% and 91.0% for the 4-IHC classification task and for the TN vs. non-TN cancers, respectively. However, for 4-IHC classification task, the accuracy of DWI with linear discriminant analysis model was 53.7% by using minor dependence emphasis on Kendall-tau-b. And for differentiating triple negative (TN) from non-TN tumours, the accuracy of DWI was 83.6% by using the maximum of variance. It indicated that the multiparametric MR radiomics performed well than DWI for 4-IHC classification task and for the TN vs. non-TN cancers.\u003c/p\u003e\n\u003cp\u003eRecently, Leithner et al apply artificial intelligence (AI) to breast cancer molecular subtyping with multiparametric MR radiomics [46]. Texture features extracted from DCE images and ADC maps and a multi-layer perceptron feed-forward artificial neural network (MLP-ANN) were used for differentiation of TN and luminal A breast cancers from other subtypes. Their results indicated that multiparametric MR radiomics could provide prognostic and predictive information derived from the entire tumour before and during treatment.\u003c/p\u003e\n\u003cp\u003eIn predicting the different statuses of IHC biomarkers, excellent diagnostic performance of radiomic features was found in differentiating between the ER-positive and -negative group, PR-positive and -negative group, HER2-positive and -negative group, and Ki-67-low and -high group. However, there were relatively low AUROCs of texture parameters in assessing the status of these biomarkers. This result may be ascribed to a small number of 18 texture parameters. Compared with our results, one study using 38 radiomic features showed a less powerful result, with AUROCs ranging from 0.641 to 0.789 in predicting ER, PR and HER2 statuses [47]. Another study showed a similar result with AUROCs ranging from 0.65 to 0.89 [14]. Therefore, radiomics-based approach can serve as a non-invasive method for predicting breast cancer receptor status.\u003c/p\u003e\n\u003cp\u003eIn our study, histogram, GLCM and RLM features had high diagnostic performance in differentiating different IHC biomarkers. For differentiating ER-positive and ER-negative cases, PR-positive and PR-negative cases, HER2-positive and HER2-negative cases, and Ki-67-low and Ki-67-high cases, the AUROCs of histogram, GLCM and RLM features were 0.963-973, 0.923-0.939, 0.902-0.974 and 0.926-0.975, respectively. Furthermore, the Fisher discriminant analysis model had high accuracy in predicting the five clinicopathological subtypes of breast cancer. We concluded that radiomic features of DWI were highly associated with IHC biomarkers and could be emerging surrogates for IHC biomarkers. With the Fisher discriminant analysis model, we provided a new radiomic approach for breast cancer subtyping, and its findings contribute to treatment selection.\u003c/p\u003e\n\u003cp\u003eOur study has some limitations. First, the main limitations of the study are its small sample size and lack of independent external validation, which makes the results difficult to reproduce in other populations. We will enlarge the sample size and apply other methods for the clinicopathological classification of breast cancer. Second, the automatic segmentation method was not applied in our study. Hence, the ROI delineation was time-consuming. Third, the apparent diffusion coefficient (ADC) value for each breast tumour was not acquired. Therefore, we failed to compare the diagnostic performance of ADC with that of radiomic features. Fourth, the lack of morphological features could limit our results. Our future work will focus on resolving these limitations.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur study demonstrated that the Fisher discriminant analysis model based on radiomic features of diffusion-weighted MRI could be used for the prediction of the clinicopathological subtypes of breast cancer with high accuracy. Moreover, the radiomic features had excellent diagnostic performance in differentiating between the ER-positive and -negative groups, PR-positive and -negative groups, HER2-positive and -negative groups, and Ki-67-low and -high groups. More breast cancer cases will be enrolled in our future work to validate this radiomic approach.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eHER2: human epidermal growth factor receptor 2\u003c/p\u003e\n\u003cp\u003eIHC: immunohistochemical\u003c/p\u003e\n\u003cp\u003eER: oestrogen receptor\u003c/p\u003e\n\u003cp\u003ePR: progesterone receptor\u003c/p\u003e\n\u003cp\u003eDWI: diffusion-weighted imaging\u003c/p\u003e\n\u003cp\u003eMRI: magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eDCE-MRI: dynamic contrast-enhanced MRI\u003c/p\u003e\n\u003cp\u003ePACS: picture archiving and communication system\u003c/p\u003e\n\u003cp\u003eROI: region of interest\u003c/p\u003e\n\u003cp\u003eVOI: volume of interest\u003c/p\u003e\n\u003cp\u003eGLSZM: grey level size zone matrix\u003c/p\u003e\n\u003cp\u003eGLCM: grey level co-occurrence matrix\u003c/p\u003e\n\u003cp\u003eRLM: run length matrix\u003c/p\u003e\n\u003cp\u003eSD: standard deviation\u003c/p\u003e\n\u003cp\u003eCWA: class-weighted accuracy\u003c/p\u003e\n\u003cp\u003eROC curve: receiver operating characteristic curve\u003c/p\u003e\n\u003cp\u003eADC: apparent diffusion coefficient\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e1. Ethics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study was approved by our institutional review board and the informed consent was waived.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2. Consent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3. Availability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4. Competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e5. Funding: \u003c/strong\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e6. Authors' contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLZM: writing, methodology, formal analysis and interpretation. NM and ZXM: methodology and writing - original draft. LJ, GY and YH: writing - original draft. LZ and ZXX: writing - review and editing. All authors have read and approved the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7. Acknowledgements: \u003c/strong\u003eNone\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e[1] American Cancer Society. Cancer Facts \u0026amp; Figures 2014. Atlanta: American Cancer Society; 2014.\u003c/p\u003e\n\u003cp\u003e[2] Perou CM, S\u0026oslash;rlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747\u0026ndash;752.\u003c/p\u003e\n\u003cp\u003e[3] Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumors. Nature. 2012;490(7418):61-70.\u003c/p\u003e\n\u003cp\u003e[4] Huber KE, Carey LA, Wazer DE. 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Applied Mathematics \u0026amp; Computation. 2014; 238(7):132-140.\u003c/p\u003e\n\u003cp\u003e[31] Volpe V, Manzoni S, Marani M, Katul G.\u0026nbsp;Leave-One-Out Cross-Validation; Springer: Berlin, Germany, 2011.\u003c/p\u003e\n\u003cp\u003e[32] Cohen G, Hilario M, Geissbuhler A. Model Selection for Support Vector Classifiers via Genetic Algorithms. An Application to Medical Decision Support. Lecture Notes in Computer Science, pp. 200\u0026ndash;211, 2004.\u003c/p\u003e\n\u003cp\u003e[33] DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach.Biometrics. 1988 sep;44(3):837-45.\u003c/p\u003e\n\u003cp\u003e[34] Sah RG, Agrwal K, Sharma U, et al. Characterization of malignant breast tissue of breast cancer patients and the normal breast tissue of healthy lactating women volunteers using diffusion MRI and in vivo 1H MR spectroscopy. J Magn Reson Imaging. 2015;41(1):169-174.\u003c/p\u003e\n\u003cp\u003e[35] Cabuk G, Nass Duce M,\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=%C3%96zg%C3%BCr%20A%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=25564776\"\u003e\u0026Ouml;zg\u0026uuml;r A\u003c/a\u003e, et al. The diagnostic value of diffusion-weighted imaging and the apparent diffusion coefficient values in the differentiation of benign and malignant breast lesions. J Med Imaging Radiat Oncol. 2015;59(2):141-148.\u003c/p\u003e\n\u003cp\u003e[36] Fujimoto H, Kazama T, Nagashima T, et al. Diffusion-weighted imaging reflects pathological therapeautic response and relapse in breast cancer. Breast Cancer. 2014;21(6):724-731.\u003c/p\u003e\n\u003cp\u003e[37] Liu S, Ren R, Chen Z, et al. Diffusion-weighted imaging in assessing pathological response of tumor in breast cancer subtype to neoadjuvant chemotherapy. J Magn Reson Imaging. 2015;42(3):779-787.\u003c/p\u003e\n\u003cp\u003e[38] Dong Y, Feng Q, Yang W, et al. Preoperative prediction of sentinel lymph node metastasis in breast cancer based on radiomics of T2-weighted fat-suppression and diffusion-weighted MRI. Eur Radiol. 2018;28(2):582-591.\u003c/p\u003e\n\u003cp\u003e[39] Bickelhauht S, Paech D, Kickingereder P, et al. Prediction of malignancy by a radiomic signature from contrast agent-free diffusion MRI in suspicious breast lesions found on screening mammography. J Magn Reson Imaging. 2017;46(2):604-616.\u003c/p\u003e\n\u003cp\u003e[40] Martincich L, Deantoni V, Bertotto I, et al. Correlations between diffusion-weighted imaging and breast cancer biomarkers. Eur Radiol. 2012;22(7):1519-1528.\u003c/p\u003e\n\u003cp\u003e[41] Grimm LJ, Zhang J, Mazurowski MA. Computational approach to radiogenomics of breast cancer: Luminal A and luminal B molecular subtypes are associated with imaging features on routine breast MRI extracted using computer vision algorithms. J Magn Reson Imaging. 2015;42(4):902-907.\u003c/p\u003e\n\u003cp\u003e[42] Waugh SA, Purdie CA, Jordan LB, et al. Magnetic resonance imaging texture analysis classification of primary breast cancer. Eur Radiol. 2016;26(2):322-330.\u003c/p\u003e\n\u003cp\u003e[43] Mazuroski MA, Zhang J, Grimm LJ, et al. Radiogenomic analysis of breast cancer: luminal B molecular subtype is associated with enhancement dynamics at MR imaging. Radiology. 2014;273(2):365-372.\u003c/p\u003e\n\u003cp\u003e[44] Leithner D, Bernard-Davila B, Martinez DF, et al. Radiomic Signatures Derived from Diffusion-Weighted Imaging for the Assessment of Breast Cancer Receptor Status and Molecular Subtypes. Mol Imaging Biol. 2020;22(2):453-461.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e[45] Xie T, Wang Z, Zhao Q, et al. Machine Learning-Based Analysis of MR Multiparametric Radiomics for the Subtype Classification of Breast Cancer. Front Oncol. 2019;9:505.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e[46] Leithner D, Mayerhoefer ME, Martinez DF, et al. Non-Invasive Assessment of Breast Cancer Molecular Subtypes with Multiparametric Magnetic Resonance Imaging Radiomics. J Clin Med. 2020;9(6):1853.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e[47] Guo W, Li H, Zhu Y, et al. Prediction of clinical phenotype in invasive breast carcinomas from the integration of radiomics and genomics data. J Med Imaging (Bellingham). 2015;2(4):041007.\u003c/p\u003e"},{"header":"Tables","content":"\u003cp style=\"margin: 0in;font-size:14px;font-family: Calibri, sans-serif;line-height: 28px;text-align: left;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10px; line-height: 32px; font-family: Verdana, Geneva, sans-serif; color: rgb(0, 0, 0);\"\u003eTable 1. Clinicopathological Subtypes and Clinical Decision-Making\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eClinicopathological Subtype\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eIHC status\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eClinical Decision-Making\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eLuminal A\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eER and/or PR positive\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHER2 negative\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eKi-67 low (\u0026lt;14%)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eEndocrine therapy\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003eLuminal B\u003csub\u003eHER2-\u003c/sub\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eER and/or PR positive\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHER2 negative\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eKi-67 high\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eEndocrine\u0026plusmn;cytotoxic therapy\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003csup\u003e\u0026amp;\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003eLuminal B\u003csub\u003eHER2+\u003c/sub\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eER and/or PR positive\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eany Ki-67\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHER2 over-expressed\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eCytotoxics + anti-HER2 + endocrine therapy\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eHER2 positive\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHER2 over-expressed\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eCytotoxics + anti-HER2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eTriple negative\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eER and PR absent\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHER2 negative\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eCytotoxics\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e*Luminal B\u003csub\u003eHER2-\u003c/sub\u003e, luminal B/HER2 negative; \u003csup\u003e\u0026amp;\u003c/sup\u003eLuminal B\u003csub\u003eHER2+\u003c/sub\u003e, luminal B/HER2 positive; IHC, immunohistochemistry\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in;font-size:14px;font-family: Calibri, sans-serif;line-height: 28px;text-align: left;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 32px;\"\u003eTable 2.\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"line-height: 32px;\"\u003e\u0026nbsp;\u003cstrong\u003eGeneral features and clinicopathological subtypes.\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 96%;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:16.1%;border-top:solid black 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:.25in;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eCharacteristic\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width:14.66%;border-top:solid black 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:.25in;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003ePatients\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e(n=112)\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" style=\"width:69.22%;border-top:solid black 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:.25in;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eClinicopathologic subtypes\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13.84%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: white;padding: 0in 5.4pt;height: 0.25in;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eLuminal A\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: white;padding: 0in 5.4pt;height: 0.25in;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eLuminal B\u003csub\u003eHER2-\u003c/sub\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: white;padding: 0in 5.4pt;height: 0.25in;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eLuminal\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eB\u003csub\u003e\u0026nbsp;HER2+\u003c/sub\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: white;padding: 0in 5.4pt;height: 0.25in;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eHER2 positive\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.86%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;background: white;padding: 0in 5.4pt;height: 0.25in;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eTriple negative\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.1%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eAge\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.66%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e46.5(25~72)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e46.1(25~69)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e47.4(32~67)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e44.6(26~69)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.92%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e45.8(28~72)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.78%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e49.5(30~61)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.1%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eER status\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.66%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.92%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.78%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.1%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Positive\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.66%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e75\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e29\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e29\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e17\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.92%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.78%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.1%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Negative\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.66%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e37\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.92%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e24\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.78%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e11\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.1%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003ePR status\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.66%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.92%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.78%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.1%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp; Positive\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.66%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e69\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e27\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e29\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e13\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.92%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.78%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.1%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp; Negative\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.66%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e43\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e4\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.92%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e24\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.78%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e11\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.1%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eHER2 status\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.66%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.92%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.78%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.1%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp; Positive\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.66%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e41\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e17\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.92%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e24\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.78%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.1%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp; Negative\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.66%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e71\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e29\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e31\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.92%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.78%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e11\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.1%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003eKi-67\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.66%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.92%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.78%;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.1%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:9.0pt;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026ge;\u0026nbsp;14%\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.66%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e81\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e31\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e16\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.92%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e23\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.78%;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e11\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.1%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;text-indent:9.0pt;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e＜\u0026nbsp;14%\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.66%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e31\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e29\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.84%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e1\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.92%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e1\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.78%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;line-height:150%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"border:none;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"border:none;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"border:none;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"border:none;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"border:none;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"border:none;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"border:none;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/td\u003e\n \u003ctd style=\"border:none;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cbr\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e \u003cstrong\u003eFisher discriminant analysis and cross-validation.\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 3.5e+2pt;border-collapse:collapse;border:none;\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 53.75pt;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;background: white;padding: 0in;height: 24.6pt;vertical-align: top;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cbr\u003e\u0026nbsp;\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 46.1pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;background: white;padding: 0in;height: 24.6pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eSubtypes/n\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 191.45pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;background: white;padding: 0in;height: 24.6pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eTraining dataset\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 62.25pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;background: white;padding: 0in;height: 24.6pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003ePrediction accuracy\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 53.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.4pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e1\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38.45pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;background: white;padding: 0in;height: 18.4pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;background: white;padding: 0in;height: 18.4pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e3\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;background: white;padding: 0in;height: 18.4pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e4\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.05pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;background: white;padding: 0in;height: 18.4pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e5\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 53.75pt;border: none;background: white;padding: 0in;height: 18.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eFisher discriminant analysis\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.1pt;border: none;background: white;padding: 0in;height: 18.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e1\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.45pt;border: none;background: white;padding: 0in;height: 18.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e28\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38.45pt;border: none;background: white;padding: 0in;height: 18.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border: none;background: white;padding: 0in;height: 18.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e1\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border: none;background: white;padding: 0in;height: 18.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.05pt;border: none;background: white;padding: 0in;height: 18.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62.25pt;border: none;background: white;padding: 0in;height: 18.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e97%\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 46.1pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e2\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.45pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38.45pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e31\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.05pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62.25pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e100%\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 46.1pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e3\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.45pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38.45pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e16\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e94%\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 46.1pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e22\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.05pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62.25pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e92%\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 46.1pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.05pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e11\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62.25pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e100%\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 53.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.95pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eTotal\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.1pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.95pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026mdash;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.95pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026mdash;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.95pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026mdash;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.95pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, 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white;padding: 0in;height: 18.95pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026mdash;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e96.4%\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 53.75pt;border: none;background: white;padding: 0in;height: 18.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eLeave-one-\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:left;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eout cross-\u0026nbsp;validation\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.1pt;border: none;background: white;padding: 0in;height: 18.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e1\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.45pt;border: none;background: white;padding: 0in;height: 18.95pt;vertical-align: top;\"\u003e\n \u003cp 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e79%\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 46.1pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e1\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.05pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e5\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e15\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e4\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.45pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd 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style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62.25pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e92%\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 46.1pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e5\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.45pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e3\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38.45pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.05pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e8\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62.25pt;border: none;background: white;padding: 0in;height: 8.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e73%\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 53.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.95pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eTotal\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.1pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.95pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026mdash;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.95pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:21.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026nbsp; \u0026nbsp; \u0026mdash;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 38.45pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.95pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:16.5pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026mdash;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.95pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:12.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026mdash;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.95pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026mdash;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.95pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026mdash;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62.25pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;background: white;padding: 0in;height: 18.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;margin-top:0in;margin-right:3.0pt;margin-left:3.0pt;line-height:16.0pt;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e82.1%\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cspan style=\"line-height: 32px;\"\u003eNote: Subtypes: 1, luminal A; 2, luminal BHER2-; 3, luminal BHer2+; 4, HER2 positive; 5, triple negative.\u003c/span\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in 21pt 0.0001pt 47.1pt;text-align: justify;font-size:14px;font-family: Calibri, sans-serif;text-indent: -47.1pt;line-height: 28px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 32px;\"\u003eTable 4. ROC analysis of radiomic features in prediction of IHC status\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eIHC status\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eRadiomic feature\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eAUROC\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eER(+) \u003cem\u003eVS.\u003c/em\u003e ER(-)\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.973 (0.949-0.997)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eTexture\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.762 (0.674-0.851)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eGLCM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.963 (0.929-0.998)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eRLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.967 (0.937-0.997)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003ePR(+) \u003cem\u003eVS.\u003c/em\u003e PR(\u0026shy;-)\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.925 (0.879-0.972)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n 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10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eGLCM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.939 (0.892-0.986)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eRLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.923 (0.875-0.971)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, 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0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.902 (0.847-0.957)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eTexture\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.722 (0.627-0.818)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n 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top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.911(0.860-0.962)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eRLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.974 (0.944-1.000)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eKi-67 low \u003cem\u003eVS.\u003c/em\u003e high\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.926 (0.870-0.981)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eTexture\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.718 (0.615-0.820)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eGLCM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.975 (0.949-1.000)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 142pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eRLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.946 (0.905-0.988)\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026nbsp;\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in;text-align: justify;font-size:14px;font-family: Calibri, sans-serif;line-height: 28px;\"\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 32px;\"\u003eTable 5.\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"line-height: 32px;\"\u003e\u0026nbsp;\u003cstrong\u003eComparison of ROC analysis results\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eIHC status\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eAUROC\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eZ statistic\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border-top: 1pt solid black;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eER(+) VS. ER(-)\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram VS. Texture\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e4.531\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: rgb(191, 191, 191);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram VS. GLCM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.462\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.644\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram VS. RLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.312\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.7548\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eTexture VS. GLCM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-4.147\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: rgb(191, 191, 191);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eTexture VS. RLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-4.322\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: rgb(191, 191, 191);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eGLCM VS. RLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-0.171\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.864\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003ePR(+) VS. PR(\u0026shy;-)\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram VS. Texture\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e3.676\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: rgb(191, 191, 191);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram VS. GLCM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-0.412\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.680\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram VS. RLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.058\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.954\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eTexture VS. GLCM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-3.941\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: rgb(191, 191, 191);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eTexture VS. RLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-3.607\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: rgb(191, 191, 191);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eGLCM VS. RLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.462\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.644\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eHER2(+) VS. HER2(-)\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram VS. Texture\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e3.189\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: rgb(191, 191, 191);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram VS. GLCM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-0.236\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.814\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram VS. RLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-2.267\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.023\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eTexture VS. GLCM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-3.407\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: rgb(191, 191, 191);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eTexture VS. RLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-4.918\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: rgb(191, 191, 191);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eGLCM VS. RLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-2.099\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: rgb(191, 191, 191);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.036\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003eKi-67 low VS. high\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram VS. Texture\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e3.493\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: rgb(191, 191, 191);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram VS. GLCM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-1.542\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.123\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eHistogram VS. RLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-0.559\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e0.576\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eTexture VS. GLCM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-4.795\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: rgb(191, 191, 191);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eTexture VS. RLM\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108.45pt;border: none;background: white;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e-4.066\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96.95pt;border: none;background: rgb(191, 191, 191);padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:center;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u0026lt;0.001\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 108.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111.9pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid black;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin:0in;margin-bottom:.0001pt;text-align:justify;font-size:14px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style=\"font-family: Verdana, Geneva, sans-serif;\"\u003e\u003cspan style=\"font-size: 10px;\"\u003eGLCM VS. 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It is simplified and can be conducted easily in clinical practice, and this subtyping undoubtedly contributes to the treatment selection of breast cancer. This study aims to investigate the feasibility of using a Fisher discriminant analysis model based on radiomic features of diffusion-weighted MRI for predicting the clinicopathological subtypes of breast cancer.\nMethods: Patients who underwent breast magnetic resonance imaging were confirmed by retrieving data from our institutional picture archiving and communication system (PACS) between March 2013 and September 2017. Five clinicopathological subtypes were determined based on the status of ER, PR, HER2 and Ki-67 from the immunohistochemical test. The radiomic features of diffusion-weighted imaging were derived from the volume of interest (VOI) of each tumour. Fisher discriminant analysis was performed for clinicopathological subtyping by using a backward selection method. To evaluate the diagnostic performance of the radiomic features, ROC analyses were performed to differentiate between immunohistochemical biomarker-positive and -negative groups.\nResults: A total of 84 radiomic features of four statistical methods were included after preprocessing. The overall accuracy for predicting the clinicopathological subtypes was 96.4% by Fisher discriminant analysis, and the weighted accuracy was 96.6%. For predicting diverse clinicopathological subtypes, the prediction accuracies ranged from 92% to 100%. According to the cross-validation, the overall accuracy of the model was 82.1%, and the accuracies of the model for predicting the luminal A, luminal BHER2-, luminal BHER2+, HER2 positive and triple negative subtypes were 79%, 77%, 88%, 92% and 73%, respectively. According to the ROC analysis, the radiomic features had excellent performance in differentiating between different statuses of ER, PR, HER2 and Ki-67.\nConclusions: The Fisher discriminant analysis model based on radiomic features of diffusion-weighted MRI is a reliable method for the prediction of clinicopathological breast cancer subtypes.","manuscriptTitle":"Prediction of the clinicopathological subtypes of breast cancer using a Fisher discriminant analysis model based on radiomic features of diffusion-weighted MRI","msid":"","msnumber":"","nonDraftVersions":[{"code":4,"date":"2020-10-26 21:19:20","doi":"10.21203/rs.2.14001/v4","editorialEvents":[{"type":"communityComments","content":0},{"type":"checksComplete","content":"","date":"2020-10-20T12:00:00+00:00","index":"","fulltext":""},{"type":"decision","content":"Accept","date":"2020-10-20T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":3,"date":"2020-10-09 20:59:23","doi":"10.21203/rs.2.14001/v3","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2020-10-05T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-09-30T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-09-29T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-09-29T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2020-05-30 14:10:34","doi":"10.21203/rs.2.14001/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-09-11T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-09-01T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nPEER REVIEWER ASSESSMENTS:\n\nOBJECTIVE - Full research articles: is there a clear objective that addresses one or several testable research questions? (Brief or other article types: is there a clear objective?)\nYes - there is a clear objective\n\nDESIGN - Is the current approach (including controls and analysis protocols) appropriate for the objective?\nNo - there are major issues\n\nEXECUTION - Are the experiments and analyses performed with sufficient technical rigor to allow confidence in the results?\nYes - experiments and analyses were performed appropriately\n\nSTATISTICS - Is the use of statistics in the manuscript appropriate?\nYes - appropriate statistical analyses have been used in the study\n\nINTERPRETATION - Is the current interpretation/discussion of the results reasonable and not overstated?\nNo - there are major issues\n\nOVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently for you to now recommend the work as a technically sound contribution? If not, can further revisions be made to make the work technically sound?\nProbably - with minor revisions\n\nPEER REVIEWER COMMENTS:\n\nGENERAL COMMENTS: The revised manuscript has improved the methods description and results presentation. Notwithstanding, there are study limitations that need to be further discussed.\n\nREQUESTED REVISIONS:\nThe main limitations of the study are its small sample size and lack of independent external validation, which makes the results difficult to reproduce in other populations. This has to be made clear in the discussion. In addition, the discussion is poor in the current format; there is a lot of repeated information from the background section and very little comparison with other published papers. Authors should compare their results with more recently published articles (e.g. doi: 10.1007/s11307-019-01383-w; 10.3389/fonc.2019.00505; 10.3390/jcm9061853) and discuss the advantages and disadvantages of their approach. It is also important to highlight the clinical significance of the findings: Is DWI radiomics better than DCE radiomics? In which situations could radiomics be used to replace or improve current IHC subtyping?\nADDITIONAL REQUESTS/SUGGESTIONS:\nRewrite discussion to address the previous commentaries.* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **No**\n* Declaration of competing interests: **This reviewer has been recruited by a partner organization, Research Square. Reviewers with declared or apparent competing interests are not utilized for these reviews. This reviewer has agreed to publication of their comments online under a Creative Commons Attribution License attributed to Research Square and was paid a small honorarium for completing the review within a specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer recommendation.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **No**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2020-07-03T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-05-22T12:00:00+00:00","index":1,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nPEER REVIEWER ASSESSMENTS:\n\nOBJECTIVE - Full research articles: is there a clear objective that addresses one or several testable research questions? (Brief or other article types: is there a clear objective?)\nYes - there is a clear objective\n\nDESIGN - Is the current approach (including controls and analysis protocols) appropriate for the objective?\nNo - there are major issues\n\nEXECUTION - Are the experiments and analyses performed with sufficient technical rigor to allow confidence in the results?\nNo - there are major issues\n\nSTATISTICS - Is the use of statistics in the manuscript appropriate?\nYes - appropriate statistical analyses have been used in the study\n\nINTERPRETATION - Is the current interpretation/discussion of the results reasonable and not overstated?\nNo - there are major issues\n\nOVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently for you to now recommend the work as a technically sound contribution? If not, can further revisions be made to make the work technically sound?\nMaybe - with major revisions\n\nPEER REVIEWER COMMENTS:\n\nGENERAL COMMENTS: Not adequately addressed. The review system cut-off part of my previous comments (which thankfully overlapped with some of reviewer 1 comments)\n\nREQUESTED REVISIONS:\nThe authors state that 'To ensure the accuracy of the model, we used the whole data set to calculate functions, and each fold was validated by leave-one-out cross validation.' This is an INCORRECT approach. Using the *entire* dataset before cross-validation results in substantial overestimation of performance and lack of generalizability. Model/function building should be performed within each training fold of the cross-validation before application to the unseen test fold.\nADDITIONAL REQUESTS/SUGGESTIONS:\nError estimates (95% confidence intervals) need to be provided for all reported performance metrics.* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **This reviewer has been recruited by a partner organization, Research Square. Reviewers with declared or apparent competing interests are not utilized for these reviews. This reviewer has agreed to publication of their comments online under a Creative Commons Attribution License attributed to Research Square and was paid a small honorarium for completing the review within a specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer recommendation.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"editorAssigned","content":"","date":"2020-05-18T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-05-18T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-05-18T12:00:00+00:00","index":1,"fulltext":""},{"type":"checksComplete","content":"","date":"2020-05-17T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-05-17T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2019-09-05 21:51:34","doi":"10.21203/rs.2.14001/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-04-20T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-04-14T12:00:00+00:00","index":2,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nPEER REVIEWER ASSESSMENTS:\n\nOBJECTIVE - Full research articles: is there a clear objective that addresses a testable research question(s) (brief or other article types: is there a clear objective)?\nYes - there is a clear objective\n\nDESIGN - Is the current approach (including controls and analysis protocols) appropriate for the objective?\nNo - there are major issues\n\nEXECUTION - Are the experiments and analyses performed with technical rigor to allow confidence in the results?\nNo - there are major issues\n\nSTATISTICS - Is the use of statistics in the manuscript appropriate?\nNo - there are issues with the statistics in the study\n\nINTERPRETATION - Is the current interpretation/discussion of the results reasonable and not overstated?\nNo - there are major issues\n\nOVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically sound? If not, can revisions be made to make the work technically sound?\nMaybe - with major revisions\n\nPEER REVIEWER COMMENTS:\n\nGENERAL COMMENTS:\n\nREQUESTED REVISIONS:\nThis is likely resulting in overestimation of performance.\n\nThe z-test is not the correct test to compare ROC curves/areas under the ROC curves (see, e.g., DeLong et al, Biometrics 1988). The comparison of AUCs also requires a correction for multiplicity.\n\nGiven the imbalance of the dataset (different prevalences of the 5 cancer subtypes) a weighted accuracy approach would give a more honest estimate of performance than a straightforward unweighted accuracy.\nADDITIONAL REQUESTS/SUGGESTIONS:\nThe authors attempt to use radiomics in the distinction between breast cancer subtypes (based on hormone receptor subtype and Ki-67). Due to the small dataset and flawed approach, however, results are extremely unlikely to generalize to new datasets.\n\nThe authors also need to address other issues in grammar, English needing a rewrite by a native speaker.* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **This reviewer has been recruited by a partner organization, Research Square. Reviewers with declared or apparent competing interests are not utilized for these reviews. This reviewer has agreed to publication of their comments online under a Creative Commons Attribution License attributed to Research Square and was paid a small honorarium for completing the review within a specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer recommendation.**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: ** I agree to the open peer review policy of the journal**\n"},{"type":"reviewerAgreed","content":"","date":"2020-03-18T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-10-08T12:00:00+00:00","index":1,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nIn \"Prediction of the clinicopathological subtypes of breast cancers using Fisher discriminant analysis model based on radiomic features of diffusion-weighted MRI,\" Ni et al. explore a radiomics method to distinguish breast cancer subtypes from DWI. The results are encouraging, but there are currently significant issues that preclude publication in the manuscript's current form. Methodological details are unclear or inconsistent, and the reporting results without cross-validation is exaggerating performance due to the effects of overfitting. Additionally, the manuscript would benefit from greater discussion motivating the authors' approach, interpreting their findings, and contextualizing this paper within the literature.\n\n- It is not appropriate to report any performance metrics that were not obtained in cross-validation. Training an 84 feature model for a sample size of 112 will surely produce an overfit model that will have artificially strong performance when evaluated on that same training data. The unusually high accuracy of the authors' approach relative to the literature is undoubtedly a result of this. Results generated outside cross-validation should be removed entirely. Any experiments performed only outside of cross-validation (e.g. feature group AUCs and comparisons) must be repeated with cross-validated predictions\n\n- Relatedly, the authors must clarify their cross-validation approach. Was the model retrained on each validation fold? Were the same set of features used for each validation fold?\n\n- The nature of this model is unclear. At several points they authors mention predicting four molecular markers: ER status, PR status, HER2 status, and Ki-67 index. However, the methods instead states that the model analyzes \"five clinicopathological subtypes of breast cancers\" and gives a set of five equations for the model. This is quite confusing, and it is not clear what is being predicted and how the performance is assessed at both the marker and subtype level.\n\n- The methods states that 84 features were incorporated into the model, but the results cites 162 after preprocessing.\n\n- The author's focus on DWI is an interesting aspect of the study, but the motivation to use DWI and its potential advantages must be more clearly articulated.\n\n- The work only cites a few examples of radiomic breast molecular subtyping from MRI and most examples are dated by a few years, however this remains an area of active investigation. The authors could better contextualize this manuscript within the literature by citing more examples of recent work in breast radiogenomics/molecular subtyping and pointing out their novel contributions in this area.\n\n- The manuscript would benefit from discussion regarding which features and expression patterns separate out each subtype/marker - what insight can these findings provide about the imaging phenotypes of clinicopathological subtypes?* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **3 \u0026 4: yes, US Patent 10,055,842 (Entropy-Based Radiogenomic Descriptors on Magnetic Resonance Imaging for Molecular Characterization of Breast Cancer) filed through university**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: ** I agree to the open peer review policy of the journal**\n"},{"type":"reviewersInvited","content":"","date":"2019-09-19T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-09-19T12:00:00+00:00","index":1,"fulltext":""},{"type":"checksComplete","content":"","date":"2019-09-01T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-08-26T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-08-25T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2019-08-24T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7bd07ac4-46e3-42fb-aee7-8705c692d12c","owner":[],"postedDate":"October 26th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":743248,"name":"Oncology"},{"id":743249,"name":"Cancer Biology"}],"tags":[],"updatedAt":"2020-11-15T15:03:27+00:00","versionOfRecord":{"articleIdentity":"rs-4701","link":"https://doi.org/10.1186/s12885-020-07557-y","journal":{"identity":"bmc-cancer","isVorOnly":false,"title":"BMC Cancer"},"publishedOn":"2020-11-09 15:01:51","publishedOnDateReadable":"November 9th, 2020"},"versionCreatedAt":"2020-10-26 21:19:20","video":"","vorDoi":"10.1186/s12885-020-07557-y","vorDoiUrl":"https://doi.org/10.1186/s12885-020-07557-y","workflowStages":[]},"version":"v4","identity":"rs-4701","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-4701","version":["v4"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}