The predictive value of contrast-enhanced ultrasound combined with ultrasonic elastography in response to neoadjuvant chemotherapy in different molecular types of breast cancer

The predictive value of contrast-enhanced ultrasound combined with ultrasonic elastography in response to neoadjuvant chemotherapy in different molecular types of breast cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The predictive value of contrast-enhanced ultrasound combined with ultrasonic elastography in response to neoadjuvant chemotherapy in different molecular types of breast cancer Yanjuan Wang, Huajie Jiao, Tao Han, Guangfei Yang, Qinglan Ke, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4213687/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective : To investigate the predictive efficacy of contrast-enhanced ultrasound (CEUS) and elastosonography (ELA) in adjuvant chemotherapy in patients with different molecular types of breast cancer. Methods : 74 patients with breast cancer from June 2021 to August 2023 were divided into Luminal A group, Luminal B group and human epidermal growth factor receptor 2 (HER-2) group according to molecular typing. All patients underwent neoadjuvant chemotherapy treatment and were divided into a reactive group (n=61 cases) and a non reactive group (n=13 cases) based on the treatment effect. All patients underwent contrast-enhanced ultrasound and ultrasound elastography (using shear wave elastography (SWE) mode) examination, and ROC curves were plotted to analyze the combined predictive performance of contrast-enhanced ultrasound and ultrasound elastography. Result : There was no statistically significant difference in the parameters of contrast-enhanced ultrasound and ultrasound elastography between the Luminal A group, Luminal B group, and HER-2 group (P>0.05); The parameters of contrast-enhanced ultrasound and ultrasound elastography after chemotherapy in breast cancer with different molecular types were lower than those before chemotherapy (P<0.05); Among 74 patients with breast cancer, 13 (17.57%) were non responsive to neoadjuvant chemotherapy. The PT, K1, and SR of the non reactive group were higher than those of the reactive group (P<0.05); The ROC curve results showed that the combined examination of contrast-enhanced ultrasound and ultrasonic elastography was more effective than the single examination in predicting the response to neoadjuvant chemotherapy in patients with different molecular types of breast cancer (P<0.05). Conclusion : When breast cancer patients are treated with neoadjuvant chemotherapy under different molecular classifications, the indexes of contrast-enhanced ultrasound and elastography have changed before and after chemotherapy, and the combination of the two has a high predictive value for different molecular classifications of breast cancer, which can obtain high sensitivity and specificity, and can provide a reliable basis for the formulation and adjustment of adjuvant therapy programs. contrast-enhanced ultrasound Ultrasound elastography Breast cancer Molecular typing Neoadjuvant chemotherapy Chemotherapy response predictive value Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Breast cancer can occur in people of different ages, which is the abnormal proliferation of breast cells caused by the human body under the joint action of a variety of factors. Patients mainly present with breast masses and nipple discharge. With the prolongation of the course of disease, the incidence of long-term metastasis will increase [1]. Neoadjuvant chemotherapy is a common intervention method for breast cancer patients, which is widely used in newly treated patients without metastasis and belongs to the category of systemic chemotherapy [2]. Neoadjuvant chemotherapy can promote downstaging of breast cancer patients, improve surgical resection rate, breast conservation rate, and improve the quality of life of patients, and most patients can benefit from it [3-4]. However, due to the different types of breast cancer, some patients are not sensitive to neoadjuvant chemotherapy drugs, which increases the toxic and side effects caused by chemotherapy and misses the opportunity of surgery [5]. Contrast-enhanced ultrasound is widely used in clinical practice, which can realize the screening and diagnosis of breast cancer [6]. Before neoadjuvant chemotherapy, the tumors of most breast cancer patients contain a large number of inflammatory cells and tumor cells. Hypoxia leads to increased density and morphological changes of collagen fibers. The above changes lead to increased hardness of the lesion tissue and higher sound wave transmission. Ultrasound elastography has a good predictive value for the pathological and prognostic factors of patients by quantifying the hardness of the lesion [8]. At the same time, hypoxia leads to the production of vascular cell endothelial factor VEGF, leading to neovascularization, increased blood vessels in the tumor, and high grading of blood flow in contrast-enhanced ultrasound. Due to the changes in tumor microenvironment after chemotherapy, treatment response can be predicted [7]. The aim of this study is to investigate the efficacy of contrast-enhanced ultrasound (CEUS) combined with ultrasound elastography in predicting the response to adjuvant chemotherapy in patients with different molecular subtypes of breast cancer. Here's the report. Materials And Methods 1.1 General Information A total of 74 patients with breast cancer from June 2021 to August 2023 were selected, aged (33-72) years, with an average of (57.11±6.76) years. The disease duration was 1-8 months, with an average of 3.26±0.51 months. The diameter of the tumor was (2.15-6.31) cm, with an average of (4.09±0.62) cm. According to the molecular classification, the patients were divided into Luminal A group (n = 30), Luminal B group (n = 26) and human epidermal growth factor receptor (HER-2) group (n = 18). According to the sensitivity of neoadjuvant chemotherapy, breast cancer was divided into response group and non-response group. There were 61 cases in the response group, aged (36-70) years, with an average of (57.11±6.78) years. The disease duration was 1-7 months, with an average of 3.32±0.56 months. The tumor diameter was (2.18-6.30) cm, with an average of (4.14±0.66) cm. There were 13 patients in the non-response group, aged from 37 to 71 years, with an average age of 56.61±6.74 years. The disease duration was (1-6) months, with an average of (3.29±0.54) months. The average diameter of the tumor was (4.04±0.59) cm (range 2.17-6.30 cm). This study was approved by the ethics committee, and patients signed the consent form. There were no significant differences in age, course of disease, and tumor volume between groups (P>0.05). 1.2 Inclusion and exclusion criteria Inclusion criteria: (1) meet the diagnostic criteria of breast cancer [9]; (2) All patients received neoadjuvant chemotherapy without allergy history and contraindications to chemotherapy drugs. (3) There were no contraindications to contrast-enhanced ultrasound and ultrasound elastography, and all patients could tolerate it. (4) all patients had complete information; Exclusion criteria: (1) patients with autoimmune diseases or advanced breast cancer with distant metastasis; (2) patients with mental disorders or malignant tumors in other parts; (3) abnormal coagulation function, pregnancy and lactation; (4) abnormal cardiopulmonary function. 1.3 Methods 1.3.1 Neoadjuvant chemotherapy All patients were treated with neoadjuvant chemotherapy, and the treatment regimen was determined according to the tumor classification of breast cancer biopsy, including: anthracycline-based CEF regimen (Cyclophosphamide (Hanhui Pharmaceutical Co., LTD., Chinese Medicine approval number H20093392, Specification: 0.2g(C7H15C12N2O2P) 600mg/m2, epirubicin (Chenxin Pharmaceutical Co., LTD., Chinese Medicine approval number H20060040, Specifications: According to C38H72N2O12 5ml:0.25g(250000 units) 75mg/m2 and 5-fluorouracil (Freenius Karbi (Wuhan) Pharmaceutical Co., LTD., Chinese Medicine approval number H20050465, Specifications: 0.125g) and TEC regimen based on paclitaxel (docetaxel (Peking Union Medical College Pharmaceutical Factory, Chinese Medicine approval number H20083786, Specifications: 10ml:60mg) 75mg/m2, cyclophosphamide 500mg/m2 and epirubicin 75mg/m2), 21 days per cycle. All patients completed 6-8 weeks of neoadjuvant chemotherapy, and underwent surgery within 1 week after the end of the course [10]. According to the treatment effect, they were divided into response group (n=61, complete remission and partial remission) and non-response group (n=13, non-complete remission and partial remission). 1.3.2 Contrast-enhanced ultrasound and ultrasound elastography were performed (1) contrast-enhanced ultrasound examination; Ceus was performed on patients after neoadjuvant chemotherapy. Philips EPIQ5 ultrasonic diagnostic instrument was used for examination, and the probe frequency was 12MHz. The imaging probe (9MH) was used to determine the accurate location of the lesion, and 2.5mL of contrast agent SonoVue was injected, with a mechanical index of 0.22. The perfusion of the lesion tissue and the surrounding tissue was recorded, and the onset time (AT), peak intensity (PI), peak time (PT) and rising slope (K1) of the lesion were recorded [11]. (2) Ultrasound elastography examination. The instrument was Aixplorer V and Aplio500 ultrasonic diagnostic instrument, and the probe frequency was L15-4MHz. After determining the accurate location of the lesion, the elastography mode was selected to ensure that the sampling range was greater than the lesion range, and the probe was placed vertically and gently above the tumor. In addition, the constant vibration of increasing and decompression was completed at the lesion site with the pressure gradient display value of 3-4 levels: it was better to keep the upper part of the SWE sampling frame without red extrusion traces. After static maintenance, the elastography was saved and the strain rate (SR) was recorded and analyzed by image post-processing software [12]. (3) Predictive efficacy. The ROC curve was drawn to analyze the predictive value of CEUS combined with ultrasound elastography for the response to neoadjuvant chemotherapy in different molecular types of breast cancer. 1.4 Statistical Analysis SPSS26.0 software was used to process the data. The enumeration data were analyzed by χ2 test, expressed by n (%), and the measurement data were analyzed by t test, expressed by (x̄ ± s ), P<0.05 was statistically significant. Results 2.1 To compare the results of contrast-enhanced ultrasound and ultrasound elastography in different molecular subtypes of breast cancer There were no significant differences in contrast-enhanced ultrasound and ultrasound elastography parameters among Luminal A group, Luminal B group and HER-2 group (P>0.05). The CEUS and ultrasound elastography parameters of different molecular types of breast cancer after chemotherapy were lower than those before chemotherapy (P<0.05), as shown in Table 1, Table 2 and Figure 1-4. Table 1 Comparison of CEUS and elastography results before chemotherapy for different molecular subtypes of breast cancer（x̄ ± s ） Molecular TYPING Number of cases AT（s） PT（s） PI（dB） K1 SR Luminal A group 30 8.96±0.81 18.68±2.14 24.83±4.48 1.83±0.14 5.31±0.52 Luminal B group 26 8.99±0.84 18.71±2.17 24.52±4.42 1.88±0.15 5.33±0.56 The HER-2 group 18 9.01±0.84 18.65±2.11 24.67±4.45 1.91±0.18 5.36±0.61 Table 2 Comparison of CEUS and elastography results before and after chemotherapy（x̄ ± s ） Molecular TYPING Number of cases AT（s） PT（s） PI（dB） K1 SR After chemotherapy 74 6.78±0.62 15.46±1.85 21.13±3.26 1.41±0.13 3.49±0.43 Before chemotherapy 74 8.98±0.83 18.69±2.15 24.71±4.43 1.87±0.16 5.34±0.51 t / 4.492 5.561 4.219 4.554 4.025 P / 0.000 0.000 0.000 0.000 0.000 Elastography images of typical cases before and after chemotherapy Note: Figure 1 shows ultrasound elastography before chemotherapy, and the SR ratio is 5.2. Figure 2 shows ultrasound elastography images after 2 cycles of chemotherapy, and the SR ratio is 3.7. Figure 3 shows ultrasound elastography images after 8 cycles of chemotherapy, and the SR ratio is 1. 2.2 Comparison of contrast-enhanced ultrasound and ultrasound elastography results between response group and non-response group of neoadjuvant chemotherapy There were 13 cases of non-response to neoadjuvant chemotherapy in 74 patients with breast cancer, accounting for 17.57%. There was no significant difference in AT and PI levels between the response group and the non-response group (P>0.05). PT, K1 and SR in the non-response group were higher than those in the response group (P<0.05), as shown in Table 3. Table 3 Comparison of contrast-enhanced ultrasound and ultrasound elastography results between the response group and the non-response group to neoadjuvant chemotherapy（x̄ ± s ） Groups Number of cases AT（s） PT（s） PI（dB） K1 SR Non-response group 13 8.97±0.82 20.53±4.36 25.19±4.51 1.89±0.16 5.37±0.56 Group of reaction 61 9.04±0.85 17.49±1.52 24.78±4.46 1.45±0.13 4.86±0.41 t / 0.548 5.524 0.241 4.118 3.452 P / 0.782 0.000 0.326 0.000 0.000 2.3 The value of different ultrasound examinations in the response of breast cancer to neoadjuvant chemotherapy The ROC curve showed that the combination of CEUS and ultrasound elastography had a higher predictive efficacy than single examination in the response to neoadjuvant chemotherapy in patients with different molecular types of breast cancer (P<0.05), as shown in Table 4 and Figure 5. Table 4 Value of different ultrasound examinations in response to neoadjuvant chemotherapy in breast cancer Variable of detection AUC Standard error P value 95% confidence interval Sensitivity Specificity Lower limit Upper limit Ultrasound elastography 0.735 0.152 0.000 0.672 0.793 70.31% 75.00% Contrast-enhanced ultrasound 0.792 0.116 0.000 0.767 0.874 82.81% 82.14% Determination of combination 0.875 0.163 .000 0.895 0.973 93.75% 92.86% Discussion As a malignant tumor with high incidence in women, breast cancer has more than 50,000 new cases every year. Most patients have no obvious clinical symptoms in the early stage of the disease, resulting in great difficulty in clinical diagnosis and treatment [13]. Neoadjuvant chemotherapy is a systemic intervention before local treatment, which has a good effect. This method can reduce the tumor stage, reduce the tumor volume, and lay the foundation for the subsequent treatment of patients [14-15]. Clinically, breast cancer is divided into four types: Luminal A, Luminal B, HER-2 and triple-negative. The triple-negative type is not included in this study because it is not sensitive to chemotherapy drugs. The shape of different types of lesions is mostly irregular, the internal is mostly hypoechoic, and the echo is uneven, the echo is strong, the boundary is not clear, and the blood flow signal is mainly grade 2 and grade 3 [16]. In this study, there was no significant difference between Luminal A group, Luminal B group and HER-2 group in contrast-enhanced ultrasound and ultrasound elastography parameters (P>0.05). According to the results, different types of breast cancer have high response to neoadjuvant chemotherapy, and there was no significant difference between the results of contrast-enhanced ultrasound and ultrasound elastography. Previous studies have shown that neoadjuvant chemotherapy can create favorable conditions for surgery or further treatment. However, for breast cancer patients with indications, different factors lead to poor treatment effect, which not only delays the timing of surgery, but also affects the long-term survival of patients [17]. In this study, there were 13 cases of non-response to neoadjuvant chemotherapy in 74 breast cancer patients, accounting for 17.57%. PT, K1 and SR in the non-response group were higher than those in the response group (P<0.05). The reason for this may be that the echo of the lesion during ultrasound diagnosis is affected by the location of the tumor, the surrounding stress and tissue specificity [18], and the echo obtained is derived from the tissue components. Before neoadjuvant chemotherapy in breast cancer patients, the lesion tissue contains a large number of inflammatory cells and tumor cells, which leads to a higher sound transmission performance than normal tissue. Moreover, the new capillaries in the tumor cells increase, and the blood flow signals of contrast-enhanced ultrasound increase. However, after neoadjuvant chemotherapy, the internal environment of the lesion site changes, elasticity and density change, tumor cells are inhibited by chemotherapy drugs, new capillaries are reduced, and contrast-enhanced ultrasound shows reduced blood flow signals, so it can accurately predict the treatment response of patients [19]. Shear wave elastography uses an instantaneous pulse to generate shear waves in vivo, and calculates the elasticity of tissues by measuring the propagation speed of shear waves. This technology is the only real-time and quantitative method to measure the Young's modulus E of local tissues. After the patient received neoadjuvant chemotherapy, the cancer cells were killed and the tissue stiffness at the lesion site was reduced. Ultrasound elastography quantifies the hardness of the lesion, and SR obtained by ultrasound elastography is an index reflecting the hardness of the lesion. The greater the hardness of the lesion, the worse the effect of neoadjuvant chemotherapy of the patient [20], which can effectively judge the pathology and prognosis of breast cancer patients. Therefore, the stiffness of different tissues can be understood by SWV measurement before and after neoadjuvant chemotherapy in breast cancer patients, and the treatment plan can be adjusted according to the measurement results, so that the patient's prognosis can be good. In this study, the indexes of contrast-enhanced ultrasound and ultrasound elastography change before and after breast cancer chemotherapy, and the images and measured values of contrast-enhanced ultrasound and ultrasound elastography can predict the effect of breast cancer chemotherapy. The combination of contrast-enhanced ultrasound and ultrasound elastography in predicting the response to neoadjuvant chemotherapy in patients with different molecular types of breast cancer was higher than that of single examination (P<0.05). The results showed that contrast-enhanced ultrasound combined with ultrasound elastography could predict the response to neoadjuvant chemotherapy in different molecular types of breast cancer. After chemotherapy, the blood flow signal in the breast cancer mass decreased and the grade decreased. The SR value of elastography decreased. This indicates that chemotherapy drugs kill tumor cells, leading to a decrease in CEUS and ultrasound elastography indicators. The combined application of the two methods, through ultrasound elastography for the differential diagnosis of the nature of the lesion, if it is a malignant tumor, there will be tissue fiber change, hardness increase phenomenon, and through the hardness change to realize the identification of the tumor boundary, so that the tumor after adjuvant chemotherapy may have decreased tumor hardness, microvascular reduction, tumor volume reduction or no significant change. However, the decrease of microvessels will change the elasticity of the tumor, and it will be affected by cell necrosis and apoptosis, which will affect the diagnostic results. Combined use of contrast-enhanced ultrasound can observe the blood flow and complete the qualitative diagnosis of the lesion, which can make up for the lack of single application of ultrasound elastography or contrast-enhanced ultrasound in the evaluation of the nature of the lesion, and can better guide the formulation of chemotherapy regimens for patients. Therefore, breast cancer patients should undergo ultrasound examination regularly during neoadjuvant chemotherapy, especially contrast-enhanced ultrasound and ultrasound elastography, to predict the development of the patient's disease. For patients who are not sensitive to chemotherapy, the plan should be adjusted as soon as possible to improve the prognosis of patients. In conclusion, when different molecular types of breast cancer patients were treated with neoadjuvant chemotherapy, the indexes of CEUS and elastography before and after chemotherapy changed. The combination of CEUS and elastography has a high predictive value for the development of different molecular types of breast cancer, and can obtain high sensitivity and specificity, which can provide a reliable basis for the formulation and adjustment of adjuvant treatment plans. Declarations Author Contribution We appreciate any sacrifice made towards ensuring that this paper is published. It is with great honor that such step will see the advancement of knowledge, understanding and experience in the practice of medicine Acknowledgement Natural Science Foundation of Ningxia, No. 2022AAC03582. References Qin Lili C, Hong K, Sijie et al (2022) The predictive value of shear wave elastography combined with AKT1 in predicting the efficacy of neoadjuvant chemotherapy and short-term prognosis in patients with locally advanced HER2-positive breast cancer[J]. 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Chin J Biomedical Eng 27(2):209–212 Bourdely P, Anselmi G, Vaivode K et al (2020) Transcriptional and Functional Analysis of CD1c + Human Dendritic Cells Identifies a CD163 + Subset Priming CD8 + CD103 + T Cells[J]. Immunity 53(2):1–18 Zhou Chengxiang L, Yabin Z, Lin et al (2021) Application of ultrasound contrast imaging combined with ultrasound elastography tissue diffusion quantitative analysis in breast cancer diagnosis[J]. Mod Progress Biomedical 21(19):3783–3786 Wanping Y, Zhijun M, Jun Z et al (2023) Value of multimodal ultrasound in the diagnosis of different molecular subtypes of breast cancer and breast hyperplasia nodules[J]. Chin Med Equip 20(4):70–75 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version 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. 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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-4213687","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":287334357,"identity":"bcf0c1fb-d6d7-4d6f-8466-56ac305062b9","order_by":0,"name":"Yanjuan 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chemotherapy\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4213687/v1/51375b74c17350940795b935.png"},{"id":54368813,"identity":"c34ce378-06f4-4e40-b595-2320448d3a01","added_by":"auto","created_at":"2024-04-09 12:57:03","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":487949,"visible":true,"origin":"","legend":"\u003cp\u003eAfter 6-8 weeks of chemotherapy\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4213687/v1/dfcaa73a8b9498448debb508.png"},{"id":54369590,"identity":"1f47330d-951e-4475-b011-deee7501dd8a","added_by":"auto","created_at":"2024-04-09 13:05:03","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":855230,"visible":true,"origin":"","legend":"\u003cp\u003eContrast-enhanced ultrasound images of typical cases\u003c/p\u003e\n\u003cp\u003eNote: The left image is the CEUS image before chemotherapy, and the right image is the CEUS image after chemotherapy. After chemotherapy, the blood flow signal in the lesion was significantly reduced.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4213687/v1/92fc13f785c0f23a4fa9ceff.png"},{"id":54368811,"identity":"87c5b74c-3b50-41ff-bf64-17331ae9280c","added_by":"auto","created_at":"2024-04-09 12:57:03","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":127104,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves of different ultrasound examinations in predicting response to neoadjuvant chemotherapy in breast cancer\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-4213687/v1/c239848cf91aa5a5ad1a9e2d.png"},{"id":55561851,"identity":"a3737528-afae-4877-ae06-c2836d1051a4","added_by":"auto","created_at":"2024-04-30 02:58:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2808700,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4213687/v1/0ae16070-614c-4605-a712-14f754db105e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The predictive value of contrast-enhanced ultrasound combined with ultrasonic elastography in response to neoadjuvant chemotherapy in different molecular types of breast cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast cancer can occur in people of different ages, which is the abnormal proliferation of breast cells caused by the human body under the joint action of a variety of factors. Patients mainly present with breast masses and nipple discharge. With the prolongation of the course of disease, the incidence of long-term metastasis will increase [1]. Neoadjuvant chemotherapy is a common intervention method for breast cancer patients, which is widely used in newly treated patients without metastasis and belongs to the category of systemic chemotherapy [2]. Neoadjuvant chemotherapy can promote downstaging of breast cancer patients, improve surgical resection rate, breast conservation rate, and improve the quality of life of patients, and most patients can benefit from it [3-4]. However, due to the different types of breast cancer, some patients are not sensitive to neoadjuvant chemotherapy drugs, which increases the toxic and side effects caused by chemotherapy and misses the opportunity of surgery [5]. Contrast-enhanced ultrasound is widely used in clinical practice, which can realize the screening and diagnosis of breast cancer [6]. Before neoadjuvant chemotherapy, the tumors of most breast cancer patients contain a large number of inflammatory cells and tumor cells. Hypoxia leads to increased density and morphological changes of collagen fibers. The above changes lead to increased hardness of the lesion tissue and higher sound wave transmission. Ultrasound elastography has a good predictive value for the pathological and prognostic factors of patients by quantifying the hardness of the lesion [8]. At the same time, hypoxia leads to the production of vascular cell endothelial factor VEGF, leading to neovascularization, increased blood vessels in the tumor, and high grading of blood flow in contrast-enhanced ultrasound. Due to the changes in tumor microenvironment after chemotherapy, treatment response can be predicted [7]. The aim of this study is to investigate the efficacy of contrast-enhanced ultrasound (CEUS) combined with ultrasound elastography in predicting the response to adjuvant chemotherapy in patients with different molecular subtypes of breast cancer. Here\u0026apos;s the report.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003e1.1 General Information \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA total of 74 patients with breast cancer from June 2021 to August 2023 were selected, aged (33-72) years, with an average of (57.11\u0026plusmn;6.76) years. The disease duration was 1-8 months, with an average of 3.26\u0026plusmn;0.51 months. The diameter of the tumor was (2.15-6.31) cm, with an average of (4.09\u0026plusmn;0.62) cm. According to the molecular classification, the patients were divided into Luminal A group (n = 30), Luminal B group (n = 26) and human epidermal growth factor receptor (HER-2) group (n = 18). According to the sensitivity of neoadjuvant chemotherapy, breast cancer was divided into response group and non-response group. There were 61 cases in the response group, aged (36-70) years, with an average of (57.11\u0026plusmn;6.78) years. The disease duration was 1-7 months, with an average of 3.32\u0026plusmn;0.56 months. The tumor diameter was (2.18-6.30) cm, with an average of (4.14\u0026plusmn;0.66) cm. There were 13 patients in the non-response group, aged from 37 to 71 years, with an average age of 56.61\u0026plusmn;6.74 years. The disease duration was (1-6) months, with an average of (3.29\u0026plusmn;0.54) months. The average diameter of the tumor was (4.04\u0026plusmn;0.59) cm (range 2.17-6.30 cm). This study was approved by the ethics committee, and patients signed the consent form. There were no significant differences in age, course of disease, and tumor volume between groups (P\u0026gt;0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.2 Inclusion and exclusion criteria\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInclusion criteria: (1) meet the diagnostic criteria of breast cancer [9]; (2) All patients received neoadjuvant chemotherapy without allergy history and contraindications to chemotherapy drugs. (3) There were no contraindications to contrast-enhanced ultrasound and ultrasound elastography, and all patients could tolerate it. (4) all patients had complete information; Exclusion criteria: (1) patients with autoimmune diseases or advanced breast cancer with distant metastasis; (2) patients with mental disorders or malignant tumors in other parts; (3) abnormal coagulation function, pregnancy and lactation; (4) abnormal cardiopulmonary function.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.3 Methods\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.3.1 Neoadjuvant chemotherapy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll patients were treated with neoadjuvant chemotherapy, and the treatment regimen was determined according to the tumor classification of breast cancer biopsy, including: anthracycline-based CEF regimen (Cyclophosphamide (Hanhui Pharmaceutical Co., LTD., Chinese Medicine approval number H20093392, Specification: 0.2g(C7H15C12N2O2P) 600mg/m2, epirubicin (Chenxin Pharmaceutical Co., LTD., Chinese Medicine approval number H20060040, Specifications: According to C38H72N2O12 5ml:0.25g(250000 units) 75mg/m2 and 5-fluorouracil (Freenius Karbi (Wuhan) Pharmaceutical Co., LTD., Chinese Medicine approval number H20050465, Specifications: 0.125g) and TEC regimen based on paclitaxel (docetaxel (Peking Union Medical College Pharmaceutical Factory, Chinese Medicine approval number H20083786, Specifications: 10ml:60mg) 75mg/m2, cyclophosphamide 500mg/m2 and epirubicin 75mg/m2), 21 days per cycle. All patients completed 6-8 weeks of neoadjuvant chemotherapy, and underwent surgery within 1 week after the end of the course [10]. According to the treatment effect, they were divided into response group (n=61, complete remission and partial remission) and non-response group (n=13, non-complete remission and partial remission).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.3.2 Contrast-enhanced ultrasound and ultrasound elastography were performed\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(1) contrast-enhanced ultrasound examination; Ceus was performed on patients after neoadjuvant chemotherapy. Philips EPIQ5 ultrasonic diagnostic instrument was used for examination, and the probe frequency was 12MHz. The imaging probe (9MH) was used to determine the accurate location of the lesion, and 2.5mL of contrast agent SonoVue was injected, with a mechanical index of 0.22. The perfusion of the lesion tissue and the surrounding tissue was recorded, and the onset time (AT), peak intensity (PI), peak time (PT) and rising slope (K1) of the lesion were recorded [11]. (2) Ultrasound elastography examination. The instrument was Aixplorer V and Aplio500 ultrasonic diagnostic instrument, and the probe frequency was L15-4MHz. After determining the accurate location of the lesion, the elastography mode was selected to ensure that the sampling range was greater than the lesion range, and the probe was placed vertically and gently above the tumor. In addition, the constant vibration of increasing and decompression was completed at the lesion site with the pressure gradient display value of 3-4 levels: it was better to keep the upper part of the SWE sampling frame without red extrusion traces. After static maintenance, the elastography was saved and the strain rate (SR) was recorded and analyzed by image post-processing software [12]. (3) Predictive efficacy. The ROC curve was drawn to analyze the predictive value of CEUS combined with ultrasound elastography for the response to neoadjuvant chemotherapy in different molecular types of breast cancer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e1.4 Statistical Analysis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSPSS26.0 software was used to process the data. The enumeration data were analyzed by \u0026chi;2 test, expressed by n (%), and the measurement data were analyzed by t test, expressed by (x̄ \u0026plusmn; \u003cem\u003es\u003c/em\u003e), P\u0026lt;0.05 was statistically significant.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e2.1 To compare the results of contrast-enhanced ultrasound and ultrasound elastography in different molecular subtypes of breast cancer\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere were no significant differences in contrast-enhanced ultrasound and ultrasound elastography parameters among Luminal A group, Luminal B group and HER-2 group (P\u0026gt;0.05). The CEUS and ultrasound elastography parameters of different molecular types of breast cancer after chemotherapy were lower than those before chemotherapy (P\u0026lt;0.05), as shown in Table 1, Table 2 and Figure 1-4.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 1 Comparison of CEUS and elastography results before chemotherapy for different molecular subtypes of breast cancer（x̄ \u0026plusmn; \u003cem\u003es\u003c/em\u003e）\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"667\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.35928143712575%\" valign=\"top\"\u003e\n \u003cp\u003eMolecular TYPING\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.029940119760479%\" valign=\"top\"\u003e\n \u003cp\u003eNumber of cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.47305389221557%\" valign=\"top\"\u003e\n \u003cp\u003eAT（s）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.67065868263473%\" valign=\"top\"\u003e\n \u003cp\u003ePT（s）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820359281437126%\" valign=\"top\"\u003e\n \u003cp\u003ePI（dB）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.323353293413174%\" valign=\"top\"\u003e\n \u003cp\u003eK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.323353293413174%\" valign=\"top\"\u003e\n \u003cp\u003eSR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.35928143712575%\" valign=\"top\"\u003e\n \u003cp\u003eLuminal A group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.029940119760479%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.47305389221557%\" valign=\"top\"\u003e\n \u003cp\u003e8.96\u0026plusmn;0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.67065868263473%\" valign=\"top\"\u003e\n \u003cp\u003e18.68\u0026plusmn;2.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820359281437126%\" valign=\"top\"\u003e\n \u003cp\u003e24.83\u0026plusmn;4.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.323353293413174%\" valign=\"top\"\u003e\n \u003cp\u003e1.83\u0026plusmn;0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.323353293413174%\" valign=\"top\"\u003e\n \u003cp\u003e5.31\u0026plusmn;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.35928143712575%\" valign=\"top\"\u003e\n \u003cp\u003eLuminal B group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.029940119760479%\" valign=\"top\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.47305389221557%\" valign=\"top\"\u003e\n \u003cp\u003e8.99\u0026plusmn;0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.67065868263473%\" valign=\"top\"\u003e\n \u003cp\u003e18.71\u0026plusmn;2.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820359281437126%\" valign=\"top\"\u003e\n \u003cp\u003e24.52\u0026plusmn;4.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.323353293413174%\" valign=\"top\"\u003e\n \u003cp\u003e1.88\u0026plusmn;0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.323353293413174%\" valign=\"top\"\u003e\n \u003cp\u003e5.33\u0026plusmn;0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.35928143712575%\" valign=\"top\"\u003e\n \u003cp\u003eThe HER-2 group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.029940119760479%\" valign=\"top\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.47305389221557%\" valign=\"top\"\u003e\n \u003cp\u003e9.01\u0026plusmn;0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.67065868263473%\" valign=\"top\"\u003e\n \u003cp\u003e18.65\u0026plusmn;2.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.820359281437126%\" valign=\"top\"\u003e\n \u003cp\u003e24.67\u0026plusmn;4.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.323353293413174%\" valign=\"top\"\u003e\n \u003cp\u003e1.91\u0026plusmn;0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.323353293413174%\" valign=\"top\"\u003e\n \u003cp\u003e5.36\u0026plusmn;0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 Comparison of CEUS and elastography results before and after chemotherapy（x̄ \u0026plusmn; \u003cem\u003es\u003c/em\u003e）\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"665\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.512048192771084%\" valign=\"top\"\u003e\n \u003cp\u003eMolecular TYPING\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.993975903614459%\" valign=\"top\"\u003e\n \u003cp\u003eNumber of cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003eAT（s）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.512048192771084%\" valign=\"top\"\u003e\n \u003cp\u003ePT（s）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.512048192771084%\" valign=\"top\"\u003e\n \u003cp\u003ePI（dB）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003eK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003eSR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.512048192771084%\" valign=\"top\"\u003e\n \u003cp\u003eAfter chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.993975903614459%\" valign=\"top\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003e6.78\u0026plusmn;0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.512048192771084%\" valign=\"top\"\u003e\n \u003cp\u003e15.46\u0026plusmn;1.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.512048192771084%\" valign=\"top\"\u003e\n \u003cp\u003e21.13\u0026plusmn;3.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003e1.41\u0026plusmn;0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003e3.49\u0026plusmn;0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.512048192771084%\" valign=\"top\"\u003e\n \u003cp\u003eBefore chemotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.993975903614459%\" valign=\"top\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003e8.98\u0026plusmn;0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.512048192771084%\" valign=\"top\"\u003e\n \u003cp\u003e18.69\u0026plusmn;2.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.512048192771084%\" valign=\"top\"\u003e\n \u003cp\u003e24.71\u0026plusmn;4.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003e1.87\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003e5.34\u0026plusmn;0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.512048192771084%\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.993975903614459%\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003e4.492\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.512048192771084%\" valign=\"top\"\u003e\n \u003cp\u003e5.561\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.512048192771084%\" valign=\"top\"\u003e\n \u003cp\u003e4.219\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003e4.554\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003e4.025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.512048192771084%\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.993975903614459%\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.512048192771084%\" valign=\"top\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.512048192771084%\" valign=\"top\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.156626506024097%\" valign=\"top\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eElastography images of typical cases before and after chemotherapy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNote: Figure 1 shows ultrasound elastography before chemotherapy, and the SR ratio is 5.2. Figure 2 shows ultrasound elastography images after 2 cycles of chemotherapy, and the SR ratio is 3.7. Figure 3 shows ultrasound elastography images after 8 cycles of chemotherapy, and the SR ratio is 1.\u003c/p\u003e\n\u003cp\u003e2.2 Comparison of contrast-enhanced ultrasound and ultrasound elastography results between response group and non-response group of neoadjuvant chemotherapy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere were 13 cases of non-response to neoadjuvant chemotherapy in 74 patients with breast cancer, accounting for 17.57%. There was no significant difference in AT and PI levels between the response group and the non-response group (P\u0026gt;0.05). PT, K1 and SR in the non-response group were higher than those in the response group (P\u0026lt;0.05), as shown in Table 3.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3 Comparison of contrast-enhanced ultrasound and ultrasound elastography results between the response group and the non-response group to neoadjuvant chemotherapy（x̄ \u0026plusmn; \u003cem\u003es\u003c/em\u003e）\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.343558282208589%\" valign=\"top\"\u003e\n \u003cp\u003eGroups\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.343558282208589%\" valign=\"top\"\u003e\n \u003cp\u003eNumber of cases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003eAT（s）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.49079754601227%\" valign=\"top\"\u003e\n \u003cp\u003ePT（s）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.49079754601227%\" valign=\"top\"\u003e\n \u003cp\u003ePI（dB）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003eK1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003eSR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.343558282208589%\" valign=\"top\"\u003e\n \u003cp\u003eNon-response group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.343558282208589%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003e8.97\u0026plusmn;0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.49079754601227%\" valign=\"top\"\u003e\n \u003cp\u003e20.53\u0026plusmn;4.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.49079754601227%\" valign=\"top\"\u003e\n \u003cp\u003e25.19\u0026plusmn;4.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003e1.89\u0026plusmn;0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003e5.37\u0026plusmn;0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.343558282208589%\" valign=\"top\"\u003e\n \u003cp\u003eGroup of reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.343558282208589%\" valign=\"top\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003e9.04\u0026plusmn;0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.49079754601227%\" valign=\"top\"\u003e\n \u003cp\u003e17.49\u0026plusmn;1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.49079754601227%\" valign=\"top\"\u003e\n \u003cp\u003e24.78\u0026plusmn;4.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003e1.45\u0026plusmn;0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003e4.86\u0026plusmn;0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.343558282208589%\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.343558282208589%\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003e0.548\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.49079754601227%\" valign=\"top\"\u003e\n \u003cp\u003e5.524\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.49079754601227%\" valign=\"top\"\u003e\n \u003cp\u003e0.241\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003e4.118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003e3.452\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.343558282208589%\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.343558282208589%\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003e0.782\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.49079754601227%\" valign=\"top\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.49079754601227%\" valign=\"top\"\u003e\n \u003cp\u003e0.326\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.110429447852761%\" valign=\"top\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003c/br\u003e\n\u003cp\u003e2.3 The value of different ultrasound examinations in the response of breast cancer to neoadjuvant chemotherapy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe ROC curve showed that the combination of CEUS and ultrasound elastography had a higher predictive efficacy than single examination in the response to neoadjuvant chemotherapy in patients with different molecular types of breast cancer (P\u0026lt;0.05), as shown in Table 4 and Figure 5.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4 Value of different ultrasound examinations in response to neoadjuvant chemotherapy in breast cancer\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"668\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.04047976011994%\" rowspan=\"2\"\u003e\n \u003cp\u003eVariable of detection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.244377811094452%\" rowspan=\"2\"\u003e\n \u003cp\u003eAUC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.84407796101949%\" rowspan=\"2\"\u003e\n \u003cp\u003eStandard error\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.944527736131935%\" rowspan=\"2\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.238380809595203%\" colspan=\"2\"\u003e\n \u003cp\u003e95% confidence interval\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.544227886056971%\" rowspan=\"2\"\u003e\n \u003cp\u003eSensitivity\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.14392803598201%\" rowspan=\"2\"\u003e\n \u003cp\u003eSpecificity\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.298701298701296%\"\u003e\n \u003cp\u003eLower limit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.701298701298704%\"\u003e\n \u003cp\u003eUpper limit\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.06906906906907%\"\u003e\n \u003cp\u003eUltrasound elastography\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.26126126126126%\"\u003e\n \u003cp\u003e0.735\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.861861861861861%\"\u003e\n \u003cp\u003e0.152\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.96096096096096%\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.861861861861861%\"\u003e\n \u003cp\u003e0.672\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.26126126126126%\"\u003e\n \u003cp\u003e0.793\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.561561561561561%\"\u003e\n \u003cp\u003e70.31%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.162162162162161%\"\u003e\n \u003cp\u003e75.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.06906906906907%\"\u003e\n \u003cp\u003eContrast-enhanced ultrasound\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.26126126126126%\"\u003e\n \u003cp\u003e0.792\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.861861861861861%\"\u003e\n \u003cp\u003e0.116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.96096096096096%\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.861861861861861%\"\u003e\n \u003cp\u003e0.767\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.26126126126126%\"\u003e\n \u003cp\u003e0.874\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.561561561561561%\"\u003e\n \u003cp\u003e82.81%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.162162162162161%\"\u003e\n \u003cp\u003e82.14%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.06906906906907%\"\u003e\n \u003cp\u003eDetermination of combination\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.26126126126126%\"\u003e\n \u003cp\u003e0.875\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.861861861861861%\"\u003e\n \u003cp\u003e0.163\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.96096096096096%\"\u003e\n \u003cp\u003e.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.861861861861861%\"\u003e\n \u003cp\u003e0.895\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.26126126126126%\"\u003e\n \u003cp\u003e0.973\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.561561561561561%\"\u003e\n \u003cp\u003e93.75%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.162162162162161%\"\u003e\n \u003cp\u003e92.86%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eAs a malignant tumor with high incidence in women, breast cancer has more than 50,000 new cases every year. Most patients have no obvious clinical symptoms in the early stage of the disease, resulting in great difficulty in clinical diagnosis and treatment [13]. Neoadjuvant chemotherapy is a systemic intervention before local treatment, which has a good effect. This method can reduce the tumor stage, reduce the tumor volume, and lay the foundation for the subsequent treatment of patients [14-15]. Clinically, breast cancer is divided into four types: Luminal A, Luminal B, HER-2 and triple-negative. The triple-negative type is not included in this study because it is not sensitive to chemotherapy drugs. The shape of different types of lesions is mostly irregular, the internal is mostly hypoechoic, and the echo is uneven, the echo is strong, the boundary is not clear, and the blood flow signal is mainly grade 2 and grade 3 [16]. In this study, there was no significant difference between Luminal A group, Luminal B group and HER-2 group in contrast-enhanced ultrasound and ultrasound elastography parameters (P\u0026gt;0.05). According to the results, different types of breast cancer have high response to neoadjuvant chemotherapy, and there was no significant difference between the results of contrast-enhanced ultrasound and ultrasound elastography. Previous studies have shown that neoadjuvant chemotherapy can create favorable conditions for surgery or further treatment. However, for breast cancer patients with indications, different factors lead to poor treatment effect, which not only delays the timing of surgery, but also affects the long-term survival of patients [17].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this study, there were 13 cases of non-response to neoadjuvant chemotherapy in 74 breast cancer patients, accounting for 17.57%. PT, K1 and SR in the non-response group were higher than those in the response group (P\u0026lt;0.05). The reason for this may be that the echo of the lesion during ultrasound diagnosis is affected by the location of the tumor, the surrounding stress and tissue specificity [18], and the echo obtained is derived from the tissue components. Before neoadjuvant chemotherapy in breast cancer patients, the lesion tissue contains a large number of inflammatory cells and tumor cells, which leads to a higher sound transmission performance than normal tissue. Moreover, the new capillaries in the tumor cells increase, and the blood flow signals of contrast-enhanced ultrasound increase. However, after neoadjuvant chemotherapy, the internal environment of the lesion site changes, elasticity and density change, tumor cells are inhibited by chemotherapy drugs, new capillaries are reduced, and contrast-enhanced ultrasound shows reduced blood flow signals, so it can accurately predict the treatment response of patients [19]. Shear wave elastography uses an instantaneous pulse to generate shear waves in vivo, and calculates the elasticity of tissues by measuring the propagation speed of shear waves. This technology is the only real-time and quantitative method to measure the Young\u0026apos;s modulus E of local tissues. After the patient received neoadjuvant chemotherapy, the cancer cells were killed and the tissue stiffness at the lesion site was reduced. Ultrasound elastography quantifies the hardness of the lesion, and SR obtained by ultrasound elastography is an index reflecting the hardness of the lesion. The greater the hardness of the lesion, the worse the effect of neoadjuvant chemotherapy of the patient [20], which can effectively judge the pathology and prognosis of breast cancer patients. Therefore, the stiffness of different tissues can be understood by SWV measurement before and after neoadjuvant chemotherapy in breast cancer patients, and the treatment plan can be adjusted according to the measurement results, so that the patient\u0026apos;s prognosis can be good.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this study, the indexes of contrast-enhanced ultrasound and ultrasound elastography change before and after breast cancer chemotherapy, and the images and measured values of contrast-enhanced ultrasound and ultrasound elastography can predict the effect of breast cancer chemotherapy. The combination of contrast-enhanced ultrasound and ultrasound elastography in predicting the response to neoadjuvant chemotherapy in patients with different molecular types of breast cancer was higher than that of single examination (P\u0026lt;0.05). The results showed that contrast-enhanced ultrasound combined with ultrasound elastography could predict the response to neoadjuvant chemotherapy in different molecular types of breast cancer. After chemotherapy, the blood flow signal in the breast cancer mass decreased and the grade decreased. The SR value of elastography decreased. This indicates that chemotherapy drugs kill tumor cells, leading to a decrease in CEUS and ultrasound elastography indicators. The combined application of the two methods, through ultrasound elastography for the differential diagnosis of the nature of the lesion, if it is a malignant tumor, there will be tissue fiber change, hardness increase phenomenon, and through the hardness change to realize the identification of the tumor boundary, so that the tumor after adjuvant chemotherapy may have decreased tumor hardness, microvascular reduction, tumor volume reduction or no significant change. However, the decrease of microvessels will change the elasticity of the tumor, and it will be affected by cell necrosis and apoptosis, which will affect the diagnostic results. Combined use of contrast-enhanced ultrasound can observe the blood flow and complete the qualitative diagnosis of the lesion, which can make up for the lack of single application of ultrasound elastography or contrast-enhanced ultrasound in the evaluation of the nature of the lesion, and can better guide the formulation of chemotherapy regimens for patients. Therefore, breast cancer patients should undergo ultrasound examination regularly during neoadjuvant chemotherapy, especially contrast-enhanced ultrasound and ultrasound elastography, to predict the development of the patient\u0026apos;s disease. For patients who are not sensitive to chemotherapy, the plan should be adjusted as soon as possible to improve the prognosis of patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn conclusion, when different molecular types of breast cancer patients were treated with neoadjuvant chemotherapy, the indexes of CEUS and elastography before and after chemotherapy changed. The combination of CEUS and elastography has a high predictive value for the development of different molecular types of breast cancer, and can obtain high sensitivity and specificity, which can provide a reliable basis for the formulation and adjustment of adjuvant treatment plans.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eWe appreciate any sacrifice made towards ensuring that this paper is published. It is with great honor that such step will see the advancement of knowledge, understanding and experience in the practice of medicine\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eNatural Science Foundation of Ningxia, No. 2022AAC03582.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eQin Lili C, Hong K, Sijie et al (2022) The predictive value of shear wave elastography combined with AKT1 in predicting the efficacy of neoadjuvant chemotherapy and short-term prognosis in patients with locally advanced HER2-positive breast cancer[J]. J Hebei Med Univ 43(11):1297\u0026ndash;1301\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu Haojie Z, Wei L, Liu et al (2022) Predictive value of ultrasound contrast-enhanced combined with HER-2 and TPS for neoadjuvant chemotherapy sensitivity in breast cancer[J]. 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Chin Med Equip 20(4):70\u0026ndash;75\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"contrast-enhanced ultrasound, Ultrasound elastography, Breast cancer, Molecular typing, Neoadjuvant chemotherapy, Chemotherapy response, predictive value","lastPublishedDoi":"10.21203/rs.3.rs-4213687/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4213687/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: To investigate the predictive efficacy of contrast-enhanced ultrasound (CEUS) and elastosonography (ELA) in adjuvant chemotherapy in patients with different molecular types of breast cancer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: 74 patients with breast cancer from June 2021 to August 2023 were divided into Luminal A group, Luminal B group and human epidermal growth factor receptor 2 (HER-2) group according to molecular typing. All patients underwent neoadjuvant chemotherapy treatment and were divided into a reactive group (n=61 cases) and a non reactive group (n=13 cases) based on the treatment effect. All patients underwent contrast-enhanced ultrasound and ultrasound elastography (using shear wave elastography (SWE) mode) examination, and ROC curves were plotted to analyze the combined predictive performance of contrast-enhanced ultrasound and ultrasound elastography.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResult\u003c/strong\u003e: There was no statistically significant difference in the parameters of contrast-enhanced ultrasound and ultrasound elastography between the Luminal A group, Luminal B group, and HER-2 group (P\u0026gt;0.05); The parameters of contrast-enhanced ultrasound and ultrasound elastography after chemotherapy in breast cancer with different molecular types were lower than those before chemotherapy (P\u0026lt;0.05); Among 74 patients with breast cancer, 13 (17.57%) were non responsive to neoadjuvant chemotherapy. The PT, K1, and SR of the non reactive group were higher than those of the reactive group (P\u0026lt;0.05); The ROC curve results showed that the combined examination of contrast-enhanced ultrasound and ultrasonic elastography was more effective than the single examination in predicting the response to neoadjuvant chemotherapy in patients with different molecular types of breast cancer (P\u0026lt;0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: When breast cancer patients are treated with neoadjuvant chemotherapy under different molecular classifications, the indexes of contrast-enhanced ultrasound and elastography have changed before and after chemotherapy, and the combination of the two has a high predictive value for different molecular classifications of breast cancer, which can obtain high sensitivity and specificity, and can provide a reliable basis for the formulation and adjustment of adjuvant therapy programs.\u003c/p\u003e","manuscriptTitle":"The predictive value of contrast-enhanced ultrasound combined with ultrasonic elastography in response to neoadjuvant chemotherapy in different molecular types of breast cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-09 12:56:58","doi":"10.21203/rs.3.rs-4213687/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c5292c34-8067-40ef-ab46-f7d0a05b2fcc","owner":[],"postedDate":"April 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-30T02:57:18+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-09 12:56:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4213687","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4213687","identity":"rs-4213687","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}