Assessing the Androgen Receptor Status in Clinicopathologic and Hematologic Characteristics of the Triple-negative Breast Cancer

Assessing the Androgen Receptor Status in Clinicopathologic and Hematologic Characteristics of the Triple-negative 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 Assessing the Androgen Receptor Status in Clinicopathologic and Hematologic Characteristics of the Triple-negative Breast Cancer Aliasghar Tirgar, Yasaman Zamanian, Fatemeh Khodadadpour Mahani, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7771474/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 Background Triple-negative breast cancer (TNBC) is an aggressive subtype with significant treatment challenges. Emerging evidence suggests that the androgen receptor (AR) may play a key role in prognosis, but findings are inconsistent. This study aimed to clarify the relationship between AR status and TNBC while examining associated clinicopathologic, hematologic, and demographic factors. Methods We analyzed AR staining in 74 TNBC cases from 250 tissue samples collected from 2017 to 2023. Patient age, tumor size, lymphovascular invasion, Ki-67 levels, and hematologic indices like mean corpuscular volume (MCV) and hemoglobin (Hb) were evaluated between AR-positive and AR-negative groups. Results Of tumors analyzed, 29.8% (22 out of 74) were AR-positive. These tumors were generally smaller, had lower Ki-67 rates, and were more common in older women. AR expression correlated significantly with MCV (p = 0.043) and Ki-67 (p = 0.014), and showed non-significant positive associations with ductal carcinoma in situ (DCIS) (p = 0.069) and lymphovascular invasion (LVI) (p = 0.055). Conclusion Our findings suggest that AR may be a useful biomarker in TNBC progression, underscoring the need for further research to assess its potential as a targeted therapeutic marker to improve treatment strategies and patient outcomes. Triple negative Breast cancer Androgen receptor Clinicopathology Hematology Figures Figure 1 Figure 2 Figure 3 Introduction Breast cancer remains the most widespread cancer globally, with triple-negative breast cancer (TNBC) representing 10–20% of cases [ 1 – 3 ] . TNBCs are characterized by lacking estrogen receptor (ER), progesterone receptor (PR), and HER2/neu (HER2R) expression, confirmed via immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) [ 2 , 4 , 5 ] .This subtype is aggressive, with poor prognosis, limited treatment options beyond chemotherapy, and variable pathological response rates (13–45%), often leading to recurrence and metastasis [ 6 – 9 ] . TNBC subtyping includes Lehmann’s classifications: basal-like 1 (BL1), basal-like 2 (BL2), mesenchymal (M), and luminal androgen receptor (LAR) [ 10 ] , later simplified to four categories [ 11 ] . While Oakman et al. identified basal (low/high immune) and LAR subtypes [ 12 ] . The frequency of Androgen receptor (AR) is estimated to be in 60–80% of all breast cancers [ 13 – 15 ] , but it is expressed in 10–43% of TNBCs [ 16 ] . Some research suggests that AR-positive TNBCs are associated with a higher rate of distant metastasis [ 17 ] and regional lymph node involvement [ 17 , 18 ] , as well as a lower rate of complete pathologic response to chemotherapy, than other types of TNBCs [ 19 , 20 ] . However, meta-analyses have indicated that AR positivity could be a favorable prognostic predictor associated with increased overall and disease-free survival and decreased relapse of tumors [ 21 – 23 ] . Nevertheless, some results have shown no clear association to confirm the prognostic effect of AR [ 24 ] .Owing to contradictory and discrepant results, it seems necessary to design a study to explore these conflicts regarding the status of AR positivity in TNBC patients to clarify its association with histopathological and other features of breast cancer tumors. Methods and Materials Study population and patients This cross-sectional study examined 74 patients diagnosed with TNBC at Kerman University of Medical Sciences Academic Hospitals in Kerman, Iran, from 2017 to 2023. the Participants were selected based on specific inclusion and exclusion criteria, with individuals lacking tumor tissue or having undergone core needle biopsies being excluded. Data collected included demographic details (age), tumor characteristics (histopathologic subtype, grade, size, necrosis, lymphovascular invasion[LVI], microcalcification, lymph node involvement, ductal carcinoma in situ [DCIS], lymphocyte infiltration rate, and Ki67), as well as hematologic indices (hemoglobin, mean corpuscular volume [MCV], and mean corpuscular hemoglobin [MCH]). Immunohistochemistry Triple-negative status was assessed using IHC staining for ER and PR, classifying results below 1% as negative. HER2 neu was considered negative with scores of 0 or 1 + without FISH amplification. An expert pathologist, blinded to patient identities, reviewed tumor tissue slides from TNBC patients who visited Afzali Pour, Shahid Bahonar, and Shafa hospitals during the study period to ensure staining viability and sample adequacy. Selected paraffin blocks were sectioned into 4-micron slices, and all TNBC slides were analyzed for AR and Ki67 expression. For AR detection, slides were prepared and placed in an oven at 70°C, followed by paraffin melting in xylene and rehydration with graded ethanols. The slides underwent treatment with Tris buffer and hydrogen peroxide before applying a primary antibody (Diagnostic BioSystems, California, USA, mouse monoclonal antibody) and incubating briefly. Secondary antibodies were applied sequentially, and after DAB chromogen application, slides were treated with hematoxylin before dehydration and mounting. The pathologist evaluated androgen receptor expression, selecting 10 high-power fields (at 40× magnification) and counting over 100 cells in each field (Fig. 1 , Fig. 3 ). TNBC samples were AR-positive if 1% or more of the nuclei were stained. [ 25 , 26 ] . Prostate tissue served as a positive control for AR staining (Fig. 2 ). For Ki67 evaluation, the same procedure was followed, with stained cells counted as a percentage of total tumor cells [ 27 , 28 ] , using a cutoff of 20% for comparison. Statistical analysis Statistical analysis was conducted using SPSS version 22.0, classifying TNBC tumors as AR-positive or AR-negative based on androgen receptor expression. We assessed the relationships between AR status and clinicopathological markers, hematologic indices, and demographic factors using chi-square tests and t-tests, with a P value under 0.05 considered significant. Means, standard deviations, and 95% confidence intervals were calculated to summarize the findings. Results Associations between AR expression and demographic parameters This study included 74 female patients with a mean age of 48.75 years (35 patients (47.2%) >50 years old vs. 30 patients (40.5%) < 50). In the AR+ group, the mean age was 51±11.2 years (8 patients (36.3%) 50), and in the AR- group, it was 47.8±12 years (27 patients (51.9%) 50). The difference in age between the two groups was not statistically significant (p-value 0.385). The patient characteristics of the AR-negative and AR-positive patients are summarized in Table 1. Table 1 : Demographic and hematologic characteristics of breast cancer patients according to AR status Variable Patients Missing a AR-(%) AR c +(%) P Value Number 74 52(70.2%) 22(29.8%) Age Mean (SD) 48.75 9 47.8(12.0 SD) 51.0(11.2 SD) 0.322 Age group < 50 35(47.2%) 27 (51.9%) 8 (36.4%) 0.385 ≥ 50 30(40.5%) 20(38.5%) 10(45.5%) Unspecified 9(12.1%) 5(9.6%) 4(18.2%) HGB, Mean (SD) 13.05 25(33.7%) 13.0 (1.5 SD) 13.2 (1.2 SD) 0.544 MCV, Mean (SD) 85.8 29(39.1%) 84.5 (6.9 SD) 88.9 (5.2 SD) 0.043 b MCH, Mean (SD) 28.51 30(40.5%) 27.8 (3.1 SD) 30.2 (3.6 SD) 0.09 Anemia 0.03 b Normocytic 4(5.4%) 4 (7.7%) Microcytic 4(5.4%) 4 (7.7%) Macrocytic 1(1.3%) 1 (4.5%) No anemia 40 31 (59.6%) 9 (40.9%) None 25 13 (25.0%) 12 (54.5%) Notes : a Some patient data may be missing from each parameter. b P-value is statistically significant. c AR positivity was defined as a 1% immunoassay in the tumor cells. Abbreviations : AR, androgen receptor; HGB, hemoglobin; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin Clinicopathologic features of TNBC and the relationship with AR status Prevalence Among the 74 samples examined in this study, 52 (70.2%) were negative for AR expression, and 22 (29.8%) were positive. The clinicopathologic feature results compared within groups are shown in Table 2. Table 2 : Pathologic characteristics of breast cancer patients according to AR status Variable Patients Missing a AR -(%) AR c +(%) P Value Tumor Size (mm) Mean (SD) 32.77 14(18.9%) 33.9(16.8 SD) 30.1(15.9 SD) 0.402 Tumor_size_category > 2 cm 14(18.9%) - 10(19.2%) 4 (18.2%) 0.986 ≤ 2 cm 46(62.1%) - 32(61.5%) 14(63.6%) Unidentified 14(18.9%) - 10(19.2%) 4(18.2%) Tumor Grade Grade2 19(25.6%) - 15(28.8%) 4 (18.2%) 0.486 Grade 3 54(72.9%) - 36(69.2%) 18(81.8%) Unidentified 1(1.3%) - 1 (1.9%) - Tumor type Invasive ductal carcinoma 61(82.4%) - 45(86.5%) 16(72.7%) 0.143 Invasive ductal carcinoma (medullary) 2(2.7%) - 2 (3.8%) - Invasive ductal and lobular 1(1.3%) - - 1 (4.5%) Invasive lobular carcinoma 1(1.3%) - - 1 (4.5%) Unidentified 9(12.1%) - 5 (9.6%) 4 (18.2%) Number of involved LN, Mean (SD) 1.97 16(21.6%) 2.3 (4.7 SD) 1.2 (2.6 SD) 0.268 LN classification 0.588 0 37(50%) 24 (46.2%) 13 (59.1%) 4 -10 6(8.1%) 4 (7.7%) 2 (9.1%) ≤ 4 12(16.2%) 10 (19.2%) 2 (9.1%) ≥ 10 3(4%) 3 (5.8%) 0 Unclassified 16(21.6%) 11 (21.2%) 5 (22.7%) DCIS 0.069 negative 35(45.9%) 25 (48.1%) 10 (45.5%) positive 30(40.5%) 18 (34.6%) 12 (54.5%) Unavailable 9(12.1%) 9 (17.3%) 0 Necrosis 0.808 negative 14(18.9%) 9 (17.3%) 5 (22.7%) positive 34(46%) 25 (48.1%) 9 (40.9%) Unavailable 26(35.1%) 18 (34.6%) 8 (36.4%) Microcalcification 0.273 negative 26(35.1%) 21 (40.4%) 5 (22.7%) positive 28(37.8%) 17 (32.7%) 11 (50.0%) Unavailable 20(27.1%) 14 (26.9%) 6 (27.3%) Vascular invasion 0.055 negative 13(17.5%) 12 (23.1%) 1 (4.5%) positive 53(71.6%) 33 (63.5%) 20 (90.9%) Unavailable 8(10.8%) 7 (13.5%) 1 (4.5%) Lymph node invasion 0.431 negative 37(50%) 24 (46.2%) 13 (59.1%) positive 22(28.3%) 17 (32.7%) 4 (18.2%) Unclassified 16(21.6%) 11 (21.2%) 5 (22.7%) Ki-67, Mean (SD) 23(31%) 57.9 (17.5 SD) 42.5 (27.8 SD) 0.091 Ki-67(%) 0.014 b ≤ 20 4(5.4%) 1 (1.9%) 3 (13.6%) > 20 47(63.5%) 38 (73.1%) 9 (40.9%) Unknown 23(31%) 13 (25.0%) 10 (45.5%) Lymphocyte infiltration 0.461 mild 21(28.3%) 12 (23.1%) 9 (40.9%) moderate 18(24.3%) 14 (26.9%) 4 (18.2%) severe 5(6.7%) 4 (7.7%) 1 (4.5%) Unclassified 30(40.5%) 22 (42.3%) 8 (36.4%) Notes : a Some patient data may be missing from each parameter. b P-value is statistically significant. c AR positivity was defined as a 1% immunoassay in the tumor cells. Abbreviations : AR, androgen receptor; LN, lymphnode; DCIS, ductal carcinoma in situ Tumor size The mean tumor size of all patients was 32.77 mm (14 patients [18.9%], 20 mm). The mean tumor size in the AR+ group was 30.1±15.9 mm, whereas it was 33.9±16.8 mm in the AR- group (P-value 0.402). In the AR+ group, 4 patients (18.2%) had masses >20 mm, and 14 patients (63.6%) had masses ≤20 mm. Among the AR- patients, 10 patients (19.2%) had tumors > 20 mm, and 32 (61.6%) patients had those ≤2 mm. The difference in tumor size between the two groups was not statistically significant (p value 0.986). Tumor grade In 19 patients (25.6%), the tumor was reported to be grade 2, and in 54 patients (72.9%), the tumor was reported to be grade 3. In the AR+ group, 4 patients (18.2%) had Grade 2 tumors, and 18 patients (81.8%) had Grade 3 tumors; in the AR- group, 15 patients (28.9%) had Grade 2 tumors, and 36 patients (69.2%) had Grade 3 tumors. The difference in tumor grade between the two groups was not statistically significant (p value 0.486). Tumor type Invasive ductal carcinoma was reported in 61 patients (82.4%). Additionally, 2 patients (2.7%) had the medullary type of invasive ductal carcinoma, while 1 patient each (1.3%) had invasive ductal carcinoma mixed with lobular carcinoma and invasive lobular carcinoma. In the AR+ group, there were 16 patients with invasive ductal carcinoma (72.8%) and 1 patient each with mixed lobular (4.5%) and lobular carcinoma (4.5%). In the AR- group, there were 45 cases of invasive ductal carcinoma (86.5%) and 2 cases of the medullary type (3.9%), with no cases of mixed lobular or lobular carcinoma. The difference between the AR+ and AR- groups was not statistically significant (p value 0.143). Lymph node metastasis The average number of lymph nodes involved in patients was 1.97, with 37 patients (50%) testing negative and 21 patients (28.3%) positive. Among the positive patients, 12 patients (16.2%) had 1 to 4 nodes, 6 patients (8.1%) had between 4 and 9 nodes, and 3 patients (4%) had more than 9 nodes. In the AR+ group, 13 patients (59.1%) were negative, and 4 (18.2%) were positive; however, in the AR- group, 24 patients (46.1%) were negative, and 17 (32.7%) were positive (P value 0.431). The average number of lymph nodes was 1.2±2.6 in AR+ patients and 2.3±4.7 in AR- patients. In the AR+ group, 13 cases (59.1%) had zero nodes, whereas in the AR- group, 24 cases (46.1%) had zero nodes. The difference in lymph node metastasis between the two groups was not statistically significant (p value 0.268). DCIS DCIS was found in 35 patients (45.9%), whereas 30 patients (40.5%) tested negative. In the AR+ group, 10 patients (45.5%) had DCIS, and 12 (54.5%) tested negative. In the AR- group, 25 patients (48.1%) tested negative, and 18 (34.6%) had DCIS. The differences between the groups were not statistically significant (p value 0.069). Necrosis Necrosis was reported in samples from 14 patients (18.9%), whereas 34 samples did not exhibit necrosis. Within the AR+ group, necrosis was observed in 5 patients (22.7%) categorized as negative and 9 patients (40.9%) as positive. In contrast, in the AR- group, necrosis occurred in 9 patients (17.3%), who were negative, and 25 patients (48.1%), who were positive. However, this difference was not statistically significant, with a p-value of 0.808. Microcalcification Among the total patients, 28 (35.1%) had microcalcifications, whereas 26 (37.8%) did not. In the AR+ group, 5 patients (22.7%) were negative, and 11 (50%) were positive for microcalcifications. In the AR- group, 21 patients (40.4%) were negative, and 17 (32.7%) were positive. The differences were not statistically significant (p value 0.273). Lymphovascular invasion LVI invasion was present in 53 patients (71.6%) and absent in 13 patients (17.5%). In the AR+ group, it was negative in 1 patient (4.5%) and positive in 20 (91%). In the AR- group, 12 patients (23.1%) were negative, and 33 (63.5%) were positive. This difference was not statistically significant (p value of 0.055). Proliferation/mitotic rate Ki-67 expression averaged 53.3% across samples. Among these samples, 4 samples (5.4%) had percentages of 20% or less, whereas 47 samples (63.5%) had percentages above 20%. The mean Ki-67 expression was 42.5% ±27.8 in the AR+ group and 57.9% ±17.5 in the AR- group (p value 0.091). In the AR+ group, 3 patients (13.6%) had Ki-67 levels of 20% or less, whereas 1 patient (1.9%) in the AR- group did. The difference in the mean expression between the groups was statistically significant (p value 0.014). Lymphocyte infiltration Lymphocyte infiltration was reported to be mild in 21 samples (28.3%), moderate in 18 samples (24.3%), and severe in 5 samples (6.7%). In the AR+ group, the lymphocyte host response was reported to be mild in 9 samples (40.9%), moderate in 4 samples (18.2%), and severe in one sample (4.5%), and in the AR- group, it was reported to be low in 12 samples (23.1%), moderate in 14 samples (26.9%), and high in 4 samples (7.7%). This difference was not statistically significant (p value 0.461). Correlations between hematologic indices and AR The patients' mean hemoglobin and MCV indices were 13.05 and 85.8, respectively, while the average MCH value was 28.51. Forty patients (81.63%) did not have anemia, whereas nine patients (12.1%) were anemic; among them, four patients (5.4%) had microcytic anemia, four patients (5.4%) had normocytic anemia, and one patient (1.3%) had macrocytic anemia. The mean hemoglobin value for patients in the AR+ group was 13.2±1.2, whereas it was 13±1.5 in the AR- group (P-value 0.544). The mean MCV value in the AR+ group was 88.9 ±5.2, and that in the AR- group was 84.5±6.9 (P-value 0.043). The mean MCH value in the AR+ group was 30.2±3.6, whereas that in the AR- group was 27.8 ±3.1 (P value 0.09). In the AR+ group, nine patients (40.9%) did not have anemia, and one patient (4.5%) had macrocytic anemia. In the AR- group, 31 patients (59.6%) were not anemic, four patients (7.7%) had microcytic anemia, and four patients (7.7%) had normocytic anemia (p-value 0.03). The differences in the MCV, anemia status, and type between the two groups were statistically significant. The hematologic characteristics of patients in the AR- and AR+ groups are summarized in Table 1. Discussion Overall role of AR in TNBC AR is a type of steroid hormone nuclear receptor that plays a role in both sexes' fertility and physiological functions, especially in terms of cell cycle proliferation, by regulating DNA transcription in malignancies [29,30] . The incidence of AR ranges from 7% to over 50% in this subtype of breast cancer [17,31,32] , with various positivity cutoff points ranging from 1% to 10% [22] . Several studies conducted in recent years have revealed different aspects of the impact of the androgen receptor on the prognosis, survival, pathological response to chemotherapy, metastasis, and recurrence of TNBC patients. In this study, we explored AR status in triple-negative female patients with breast cancer and its relevance to age, clinicopathologic, and hematologic parameters. Prevalence and selection of the cutoff point for AR positivity Currently, there is no standard protocol to evaluate AR positivity via IHC, so we used 1% as the cutoff, similar to many recent studies [17,32,33] . Some studies have used 5% [34] or 10% [35–37] , particularly in a few clinical studies that demonstrated the beneficial effect of anti-androgen therapy in patients with metastatic disease [38] . Additionally, this threshold is the standard for the estrogen and progesterone scoring system according to the ASCO/CAP guidelines [39,40] . Among the 74 TNBCs examined in our study, 29.7% (22:74) of the TNBC tumors expressed the AR receptor, whereas 70.3% (52:74) had quadruple-negative breast cancer. Our findings concur with the range of most research investigating AR expression via the same method and threshold [41–43] . On the other hand, the results of some studies did not align with our findings, with higher and lower rates of positivity ranging from 13% to 63% [17,19,26,44,45] . These wide ranges of differing findings suggest that a probable factor influencing AR expression in TNBC worldwide is the diversity in demographic, racial, and ethnic characteristics of the target population [26] . Associations between AR and patient characteristics Our study found a mean diagnosis age of 48.7 years, with AR+ (51 years) older than AR- (47.8 years) patients, but not statistically significant. This differs from Dubrava et al., who reported significant age differences (47–69 years) in 137 TNBC samples at a 10% AR cutoff. A Japanese study demonstrated a positive relationship between older age and lower recurrence rate in AR+ TNBC patients [45] . Relationships of AR with clinicopathologic parameters No significant differences in clinicopathologic features (tumor size, lymphocytic infiltration, lymph node invasion, microcalcification, necrosis, tumor grade, tumor type, DCIS, LVI) were found between AR+ and AR- groups. However, DCIS and LVI showed non-significant but meaningful trend (p=0.055, p=0.066, 0.05<p<0.1), with higher LVI (95% vs. 73%) and DCIS (54% vs. 41%) in AR+ vs. AR- tissues. Larger samples may yield significance. Overall, explorations emphasize the poor prognostic effect of LVI on overall survival (OS) and disease-free survival (DFS) in TNBC patients [44,46,47] . Merckx et al. reported higher DCIS in AR+ patients with variable relapse effects [48] . Conversely, American studies found an inverse DCIS-AR link in TNBC [36,45] . AR’s prognostic role in TNBC varies. A meta-analysis of 2826 cases linked AR positivity to better DFS, not OS [17,22] . A 2021 study between 75 TNBC patients found AR as an independent predictor of better outcomes, especially in older patients. Adamo et al. reported poorer OS and DFS in AR- patients (n=121), tying low AR to metastasis [42,49] . Some studies linked AR+ to similar outcomes, such as a 2024 study that found no AR-prognosis link in TNBC, reflecting varied findings across nationalities. [26] . AR’s prognostic role in TNBC remains debated. AR and Proliferation Rate Indicator Correlations In our study, the mean Ki-67 index was 55.4% (AR-/AR+, 57.9:42.5) in all TNBC tumors. Our results revealed a trend toward lower mitotic scores in the AR+ group than in the AR- group at a cutoff of 20%, with a statistically significant difference (p value 0.014). This finding aligns with the majority of research in this field; for example, Dicei and colleagues, along with Leone et al., reported that TNBC patient tumors expressing AR exhibited a lower mitotic rate [19,43] . The prognostic role of Ki-67 has been investigated and identified as a valuable marker; a study on TNBCs in 2017 revealed that Ki-67 expression above 20% was significantly associated with poor outcomes [49] and A study involving 1800 patients in China showed that Ki-67 could serve as a prognostic indicator beyond a 30% cutoff, correlating with worse OS and DFS, and highlighted that patients treated with adjuvant chemotherapy had longer OS than those with low Ki-67 [50] , and the same result was reported for a 40% cutoff in meta-analysis research, which included 35 studies with 7716 enrolled patients [51] . Furthermore, an exploration of clinicopathologic evaluations by Urru and colleagues revealed a significant increase in the mortality rate associated with Ki-67 greater than 16% in triple-negative breast cancers [52] . On the other hand, some studies exploring Ki-67 as a prognostic marker did not find significant differences between AR+ and AR- patients at a 50% threshold. Nevertheless, there appears to be an inverse correlation between Ki-67 and AR positivity, which has been reported in most of the studies. AR and Hematologic Index associations The microcytic anemia was present in both groups, with statistically significant findings. Notably, the mean hemoglobin level and mean MCV were greater in the AR-positive group. Various factors, including chemotherapy complications, tumor-induced bleeding, and chronic inflammatory conditions, can cause anemia in TNBC patients. While few studies have been conducted on this topic, hemoglobin levels are generally low in patients with breast cancer [53,54] . However, the incidental finding of increased mean hemoglobin and MCV in the AR-positive group provides an opportunity to clarify hypotheses related to this phenomenon. Androgens, particularly testosterone, influence erythropoiesis by stimulating erythropoietin activity and enhancing red blood cell production [53] . Additionally, androgens may directly affect hematopoietic stem cells within the bone marrow, promoting erythrocyte production. Previous studies have demonstrated the beneficial effects of androgens in treating anemia in patients with aplastic anemia and other bone marrow failure disorders [55,56] . Specifically, research focusing on women with congenital adrenal hyperplasia has shown that androgens can positively impact hemoglobin and hematocrit (Hct) levels [57] . Examining the trajectory of testosterone in cancer treatment reveals significant findings. In prostate cancer patients receiving androgen deprivation therapy, which is often facilitated by agents such as abiraterone acetate, anemia is a notable side effect. These results can be explained by the above mechanisms [58] . Therefore, while hormonal therapies are not a treatment option for TNBC patients, as they are for other subtypes, the effects of androgen receptor presence can be explained through its potential to stimulate erythropoiesis and influence bone marrow function. Given that no prior studies have investigated this specific issue and that our findings emerged accidentally, further systematic research is needed to validate these hypotheses. Conclusion Our findings demonstrated that approximately 29% of TNBC patients expressed AR, and a statistically significant relationship was found between Ki67, a proliferative index of the tumor, and AR, MCV, and Hemoglobin. We found no associations with clinicopathologic or demographic characteristics; however, there were meaningful but insignificant results regarding DCIS and LVI. Our findings align with previous studies and lay the groundwork for future research. These results emphasize the importance of AR expression in managing TNBC. AR status could aid in developing personalized treatment strategies, distinguishing between AR-positive and AR-negative TNBC. We recommend conducting further clinical evaluations with a larger sample size and implementing a prediction model for AR to clarify its prognostic role in TNBC and improve therapeutic options. We hope our survey aids in addressing challenges in this field. Limitations This study has several limitations. First, the sample size from 2017 to 2023 was inadequate for accurate prevalence estimation, which may affect the generalizability of our findings. Additionally, relying on medical records for clinicopathological data can introduce biases due to varying quality of information. While IHC is a common method for assessing AR expression, differences in staining techniques may impact the consistency of results. Declarations Acknowledgment We are thankful to Mrs. Rashidi at the Kerman Pathology Research Center for her support in conducting the IHC method and to Dr. Rezaie for performing the statistical analysis of our findings. Additionally, we extend our appreciation to all individuals who contributed to this research, including those who helped with sample collection, provided kits, and offered scientific guidance throughout the writing of this article. Contributions Aliasghar Tirgar was involved in the design, coordination, and conceptualization of the study, as well as sample collection, data interpretation, and manuscript drafting. Yasamin Zamanian, Yasaman Mousavi, and Fatemeh Khodadadpour Mahani contributed to sample collection, interpretation of the findings, and drafting of the manuscript. Fatemeh Fathi and Fatemeh Nakhaie participated in sample collection. Vahid Moazed, Mohammad Khaksari, and Elham Jafari provided expert supervision in their respective fields of medical oncology, physiology, and pathology. All authors reviewed and approved the final version of the manuscript. Funding sources This work was supported by grants from the Kerman University of Medical Sciences, Kerman, Iran (Grant No. 400000061). Availability of data and materials The datasets used and/or analyzed in the present study are available from the corresponding author upon reasonable request. Consent to publish We hereby give our consent for the publication of the manuscript, along with all accompanying images and data that may disclose our identities. We understand that this information will be publicly accessible online and may be reproduced in accordance with the terms established by Discover Oncology, which could affect our privacy. We have reviewed the manuscript before publication and acknowledge that it won't be possible to remove it from the record except under extraordinary circumstances. Competing Interests The authors do not have any competing financial/non-financial interests. Ethics approval and consent to participate This research followed the principles outlined in the Declaration of Helsinki and received approval from the Ethics Committee of Kerman University of Medical Sciences (Ethics code: IR.KMU.AH.REC.1400.191). The requirement for informed consent was waived by the ethics committee/IRB of Kerman University of Medical Sciences due to the retrospective nature of the study and the de-identification of patient information. References Elengoe A. A Short Review on Breast Cancer. Int J Biotechnol Biomed 2024;1(1):1–11. Lee KL, Kuo YC, Ho YS, Huang YH. Triple-negative breast cancer: current understanding and future therapeutic breakthrough targeting cancer stemness. 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Abstract PO5-03-10: The prognostic role of androgen receptor status in patients with triple negative breast cancer with an associated ductal carcinoma in situ. Cancer Res [Internet] 2024;84(9_Supplement):PO5-03-10-PO5-03–10. Available from: https://doi.org/10.1158/1538-7445.SABCS23-PO5-03-10 Adamo B, Ricciardi GRR, Ieni A, Franchina T, Fazzari C, Sanò MV, et al. The prognostic significance of combined androgen receptor, E-Cadherin, Ki67 and CK5/6 expression in patients with triple negative breast cancer. Oncotarget 2017;8(44):76974. Zhu X, Chen L, Huang B, Wang Y, Ji L, Wu J, et al. The prognostic and predictive potential of Ki-67 in triple-negative breast cancer. Sci Rep 2020;10(1):225. Wu Q, Ma G, Deng Y, Luo W, Zhao Y, Li W, et al. Prognostic value of Ki-67 in patients with resected triple-negative breast cancer: a meta-analysis. Front Oncol 2019;9:1068. Urru SAM, Gallus S, Bosetti C, Moi T, Medda R, Sollai E, et al. Clinical and pathological factors influencing survival in a large cohort of triple-negative breast cancer patients. BMC Cancer 2018;18(1):56. Warren AM, Grossmann M. Haematological actions of androgens. Best Pract Res Clin Endocrinol Metab 2022;36(5):101653. Sharma P, Georgy JT, Andrews AG, John AO, Joel A, Chacko RT, et al. Anemia requiring transfusion in breast cancer patients on dose-dense chemotherapy: Prevalence, risk factors, cost and effect on disease outcome. Support Care Cancer 2022;30(6):5519–26. Nassani M, Fakih R El, Passweg J, Cesaro S, Alzahrani H, Alahmari A, et al. The role of androgen therapy in acquired aplastic anemia and other bone marrow failure syndromes. Front Oncol 2023;13:1135160. Pagliuca S, Kulasekararaj AG, Eikema DJ, Piepenbroek B, Iftikhar R, Satti TM, et al. Current use of androgens in bone marrow failure disorders: a report from the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica 2023;109(3):765. Karunasena N, Han TS, Mallappa A, Elman M, Merke DP, Ross RJM, et al. Androgens correlate with increased erythropoiesis in women with congenital adrenal hyperplasia. Clin Endocrinol (Oxf) 2017;86(1):19–25. Grossmann M, Zajac JD. Hematological changes during androgen deprivation therapy. Asian J Androl 2012;14(2):187. 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. 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. 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1","display":"","copyAsset":false,"role":"figure","size":341424,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eHematoxylin and Eosin Staining of TNBC tissue\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7771474/v1/05ac89c4b8a783354e041f80.png"},{"id":95807704,"identity":"00715a45-82a1-4bb0-9ef1-d9bd5cd4eb32","added_by":"auto","created_at":"2025-11-13 08:49:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":252209,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u0026nbsp;prostate tissue as a positive control for AR staining\u003c/em\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7771474/v1/1fd3ee5c468259b2689a06ee.png"},{"id":95807800,"identity":"42cca641-2072-40ec-bd79-4bd06190783e","added_by":"auto","created_at":"2025-11-13 08:49:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":516945,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003e(A,C)\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e AR-positive TNBC Cancer Sample via IHC(40\u003c/em\u003e×\u003cem\u003e, 10\u003c/em\u003e× \u003cem\u003emagnification)\u003c/em\u003e\u003cem\u003e\u003cstrong\u003e(B,D) \u003c/strong\u003e\u003c/em\u003e\u003cem\u003eAR-negative TNBC via IHC (40\u003c/em\u003e×\u003cem\u003e, 10\u003c/em\u003e×\u003cem\u003e magnification)\u003c/em\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7771474/v1/058368cd7dc617d9a446ac60.png"},{"id":99686926,"identity":"58c978cb-8d04-4394-adc1-ed60c7cded36","added_by":"auto","created_at":"2026-01-07 09:40:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1951616,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7771474/v1/f2737a97-18e0-4a60-ab6d-6a9b7d0c07ff.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Assessing the Androgen Receptor Status in Clinicopathologic and Hematologic Characteristics of the Triple-negative Breast Cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast cancer remains the most widespread cancer globally, with triple-negative breast cancer (TNBC) representing 10\u0026ndash;20% of cases\u003csup\u003e[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. TNBCs are characterized by lacking estrogen receptor (ER), progesterone receptor (PR), and HER2/neu (HER2R) expression, confirmed via immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH)\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.This subtype is aggressive, with poor prognosis, limited treatment options beyond chemotherapy, and variable pathological response rates (13\u0026ndash;45%), often leading to recurrence and metastasis\u003csup\u003e[\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. TNBC subtyping includes Lehmann\u0026rsquo;s classifications: basal-like 1 (BL1), basal-like 2 (BL2), mesenchymal (M), and luminal androgen receptor (LAR)\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e, later simplified to four categories\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. While Oakman et al. identified basal (low/high immune) and LAR subtypes\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. The frequency of Androgen receptor (AR) is estimated to be in 60\u0026ndash;80% of all breast cancers\u003csup\u003e[\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, but it is expressed in 10\u0026ndash;43% of TNBCs\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eSome research suggests that AR-positive TNBCs are associated with a higher rate of distant metastasis\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e and regional lymph node involvement\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e, as well as a lower rate of complete pathologic response to chemotherapy, than other types of TNBCs\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. However, meta-analyses have indicated that AR positivity could be a favorable prognostic predictor associated with increased overall and disease-free survival and decreased relapse of tumors\u003csup\u003e[\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. Nevertheless, some results have shown no clear association to confirm the prognostic effect of AR\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e.Owing to contradictory and discrepant results, it seems necessary to design a study to explore these conflicts regarding the status of AR positivity in TNBC patients to clarify its association with histopathological and other features of breast cancer tumors.\u003c/p\u003e"},{"header":"Methods and Materials","content":"\u003cp\u003eStudy population and patients\u003c/p\u003e\u003cp\u003e This cross-sectional study examined 74 patients diagnosed with TNBC at Kerman University of Medical Sciences Academic Hospitals in Kerman, Iran, from 2017 to 2023. the Participants were selected based on specific inclusion and exclusion criteria, with individuals lacking tumor tissue or having undergone core needle biopsies being excluded. Data collected included demographic details (age), tumor characteristics (histopathologic subtype, grade, size, necrosis, lymphovascular invasion[LVI], microcalcification, lymph node involvement, ductal carcinoma in situ [DCIS], lymphocyte infiltration rate, and Ki67), as well as hematologic indices (hemoglobin, mean corpuscular volume [MCV], and mean corpuscular hemoglobin [MCH]).\u003c/p\u003e\u003cp\u003eImmunohistochemistry\u003c/p\u003e\u003cp\u003eTriple-negative status was assessed using IHC staining for ER and PR, classifying results below 1% as negative. HER2 neu was considered negative with scores of 0 or 1\u0026thinsp;+\u0026thinsp;without FISH amplification. An expert pathologist, blinded to patient identities, reviewed tumor tissue slides from TNBC patients who visited Afzali Pour, Shahid Bahonar, and Shafa hospitals during the study period to ensure staining viability and sample adequacy.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eSelected paraffin blocks were sectioned into 4-micron slices, and all TNBC slides were analyzed for AR and Ki67 expression. For AR detection, slides were prepared and placed in an oven at 70\u0026deg;C, followed by paraffin melting in xylene and rehydration with graded ethanols. The slides underwent treatment with Tris buffer and hydrogen peroxide before applying a primary antibody (Diagnostic BioSystems, California, USA, mouse monoclonal antibody) and incubating briefly. Secondary antibodies were applied sequentially, and after DAB chromogen application, slides were treated with hematoxylin before dehydration and mounting.\u003c/p\u003e\u003cp\u003eThe pathologist evaluated androgen receptor expression, selecting 10 high-power fields (at 40\u0026times; magnification) and counting over 100 cells in each field (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003e). TNBC samples were AR-positive if 1% or more of the nuclei were stained.\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. Prostate tissue served as a positive control for AR staining (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFor Ki67 evaluation, the same procedure was followed, with stained cells counted as a percentage of total tumor cells\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e, using a cutoff of 20% for comparison.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eStatistical analysis was conducted using SPSS version 22.0, classifying TNBC tumors as AR-positive or AR-negative based on androgen receptor expression. We assessed the relationships between AR status and clinicopathological markers, hematologic indices, and demographic factors using chi-square tests and t-tests, with a P value under 0.05 considered significant. Means, standard deviations, and 95% confidence intervals were calculated to summarize the findings.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAssociations between AR expression and demographic parameters\u003c/p\u003e\n\u003cp\u003eThis study included 74 female patients with a mean age of 48.75 years (35 patients (47.2%) \u0026gt;50 years old vs. 30 patients (40.5%) \u0026lt; 50). In the AR+ group, the mean age was 51\u0026plusmn;11.2 years (8 patients (36.3%) \u0026lt; 50 years of age vs. 10 patients (45.5%) \u0026gt; 50), and in the AR- group, it was 47.8\u0026plusmn;12 years (27 patients (51.9%) \u0026lt; 50 years of age and 20 patients (38.5%) \u0026gt; 50). The difference in age between the two groups was not statistically significant (p-value 0.385). The patient characteristics of the AR-negative and AR-positive patients are summarized in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eDemographic and hematologic characteristics of breast cancer patients according to AR status\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"717\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003ePatients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003eMissing \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003eAR-(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003eAR\u003csup\u003ec\u003c/sup\u003e+(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eP Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eNumber\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e52(70.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e22(29.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e48.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e47.8(12.0 SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e51.0(11.2 SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.322\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eAge group\u003c/p\u003e\n \u003cp\u003e\u0026lt; 50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e35(47.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27\u0026nbsp;(51.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8\u0026nbsp;(36.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.385\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u0026ge; 50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e30(40.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e20(38.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e10(45.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eUnspecified\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e9(12.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e5(9.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e4(18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eHGB, Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e13.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e25(33.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e13.0 (1.5 SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e13.2 (1.2 SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0.544\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eMCV, Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e85.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e29(39.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e84.5 (6.9 SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e88.9 (5.2 SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.043\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eMCH, Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e28.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e30(40.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e27.8 (3.1 SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e30.2 (3.6 SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eAnemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u0026nbsp;Normocytic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e4(5.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e4 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u0026nbsp;Microcytic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e4(5.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e4 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u0026nbsp;Macrocytic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e1(1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e1 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u0026nbsp;No anemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e31 (59.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e9 (40.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u0026nbsp;None\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 97px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e13 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\n \u003cp\u003e12 (54.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNotes\u003c/strong\u003e: \u003csup\u003ea\u0026nbsp;\u003c/sup\u003eSome patient data may be missing from each parameter. \u003csup\u003eb\u0026nbsp;\u003c/sup\u003eP-value is statistically significant. \u003csup\u003ec\u0026nbsp;\u003c/sup\u003eAR positivity was defined as a 1% immunoassay in the tumor cells.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: AR, androgen receptor; HGB, hemoglobin; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin\u003c/p\u003e\n\u003cp\u003eClinicopathologic features of TNBC and the relationship with AR status\u003c/p\u003e\n\u003cp\u003ePrevalence\u003c/p\u003e\n\u003cp\u003eAmong the 74 samples examined in this study, 52 (70.2%) were negative for AR expression, and 22 (29.8%) were positive. The clinicopathologic feature results compared within groups are shown in Table 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003ePathologic characteristics of breast cancer patients according to AR status\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"700\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003ePatients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003eMissing\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eAR -(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eAR\u003csup\u003ec\u003c/sup\u003e +(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003eP Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eTumor Size (mm)\u003c/p\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14(18.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e33.9(16.8 SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e30.1(15.9 SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.402\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eTumor_size_category\u003c/p\u003e\n \u003cp\u003e\u0026gt; 2 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14(18.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10(19.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.986\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026le; 2 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e46(62.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e32(61.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e14(63.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eUnidentified\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e14(18.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e10(19.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e4(18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eTumor Grade\u003c/p\u003e\n \u003cp\u003eGrade2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19(25.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15(28.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.486\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eGrade 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e54(72.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e36(69.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e18(81.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eUnidentified\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e1(1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e1 (1.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eTumor type\u003c/p\u003e\n \u003cp\u003eInvasive ductal carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e61(82.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e45(86.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16(72.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.143\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eInvasive ductal carcinoma (medullary)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e2(2.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e2 (3.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eInvasive ductal and lobular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e1(1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e1 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eInvasive lobular carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e1(1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e1 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eUnidentified\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e9(12.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e5 (9.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e4 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eNumber of involved LN, Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e1.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e16(21.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e2.3 (4.7 SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e1.2 (2.6 SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e0.268\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eLN classification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"6\" style=\"width: 128px;\"\u003e\n \u003cp\u003e0.588\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e37(50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e24 (46.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e13 (59.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;4 -10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e6(8.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e4 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e2 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026le; 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e12(16.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e10 (19.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e2 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026ge; 10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e3(4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e3 (5.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;Unclassified\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e16(21.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e11 (21.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e5 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eDCIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 128px;\"\u003e\n \u003cp\u003e0.069\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e35(45.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e25 (48.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e10 (45.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e30(40.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e18 (34.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e12 (54.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;Unavailable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e9(12.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e9 (17.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eNecrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 128px;\"\u003e\n \u003cp\u003e0.808\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e14(18.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e9 (17.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e5 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e34(46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e25 (48.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e9 (40.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;Unavailable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e26(35.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e18 (34.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e8 (36.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eMicrocalcification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 128px;\"\u003e\n \u003cp\u003e0.273\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e26(35.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e21 (40.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e5 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e28(37.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e17 (32.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e11 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;Unavailable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e20(27.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e14 (26.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e6 (27.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eVascular invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 128px;\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e13(17.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e12 (23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e1 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e53(71.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e33 (63.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e20 (90.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp; Unavailable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e8(10.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e7 (13.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e1 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eLymph node invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 128px;\"\u003e\n \u003cp\u003e0.431\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e37(50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e24 (46.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e13 (59.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e22(28.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e17 (32.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e4 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;Unclassified\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e16(21.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e11 (21.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e5 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eKi-67, Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e23(31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e57.9 (17.5 SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e42.5 (27.8 SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e0.091\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eKi-67(%)\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 128px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.014\u003csup\u003eb\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026le; 20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e4(5.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e1 (1.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e3 (13.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026gt; 20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e47(63.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e38 (73.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e9 (40.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;Unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e23(31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e13 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e10 (45.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003eLymphocyte infiltration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\" style=\"width: 128px;\"\u003e\n \u003cp\u003e0.461\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;mild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e21(28.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e12 (23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e9 (40.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;moderate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e18(24.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e14 (26.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e4 (18.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;severe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e5(6.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e4 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e1 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;Unclassified\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e30(40.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e22 (42.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003e8 (36.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNotes\u003c/strong\u003e: \u003csup\u003ea\u0026nbsp;\u003c/sup\u003eSome patient data may be missing from each parameter. \u003csup\u003eb\u0026nbsp;\u003c/sup\u003eP-value is statistically significant.\u0026nbsp;\u003csup\u003ec\u0026nbsp;\u003c/sup\u003eAR positivity was defined as\u0026nbsp;a\u0026nbsp;1% immunoassay in the tumor cells.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: AR, androgen receptor; LN, lymphnode; DCIS, ductal carcinoma in situ\u003c/p\u003e\n\u003cp\u003eTumor size\u003c/p\u003e\n\u003cp\u003eThe mean tumor size of all patients was 32.77 mm (14 patients [18.9%], \u0026lt; 20 mm, and 46 patients [62.1%]\u0026gt; 20 mm). The mean tumor size in the AR+ group was 30.1\u0026plusmn;15.9 mm, whereas it was 33.9\u0026plusmn;16.8 mm in the AR- group (P-value 0.402). In the AR+ group, 4 patients (18.2%) had masses \u0026gt;20 mm, and 14 patients (63.6%) had masses \u0026le;20 mm. Among the AR- patients, 10 patients (19.2%) had tumors \u0026gt; 20 mm, and 32 (61.6%) patients had those \u0026le;2 mm. The difference in tumor size between the two groups was not statistically significant (p value 0.986).\u003c/p\u003e\n\u003cp\u003eTumor grade\u003c/p\u003e\n\u003cp\u003eIn 19 patients (25.6%), the tumor was reported to be grade 2, and in 54 patients (72.9%), the tumor was reported to be grade 3. In the AR+ group, 4 patients (18.2%) had Grade 2 tumors, and 18 patients (81.8%) had Grade 3 tumors; in the AR- group, 15 patients (28.9%)\u0026nbsp;had Grade 2 tumors, and 36 patients (69.2%) had Grade 3 tumors. The difference in tumor grade between the two groups was not statistically significant (p value 0.486).\u003c/p\u003e\n\u003cp\u003eTumor type\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Invasive ductal carcinoma was reported in 61 patients (82.4%). Additionally, 2 patients (2.7%) had the medullary type of invasive ductal carcinoma, while 1 patient each (1.3%) had invasive ductal carcinoma mixed with lobular carcinoma and invasive lobular carcinoma. In the AR+ group, there were 16\u0026nbsp;patients with\u0026nbsp;invasive ductal carcinoma (72.8%) and 1\u0026nbsp;patient\u0026nbsp;each\u0026nbsp;with\u0026nbsp;mixed lobular (4.5%) and lobular carcinoma (4.5%). In the AR- group, there were 45 cases of invasive ductal carcinoma (86.5%) and 2 cases of\u0026nbsp;the\u0026nbsp;medullary type (3.9%), with no cases of mixed lobular or lobular carcinoma. The\u0026nbsp;difference\u0026nbsp;between the AR+ and AR- groups was not statistically significant (p\u0026nbsp;value 0.143).\u003c/p\u003e\n\u003cp\u003eLymph node metastasis\u003c/p\u003e\n\u003cp\u003eThe average number of lymph nodes involved in patients was 1.97, with 37 patients (50%) testing negative and 21 patients (28.3%) positive. Among the positive patients, 12 patients (16.2%) had 1 to 4 nodes, 6 patients (8.1%) had between 4 and 9 nodes, and 3 patients (4%) had more than 9 nodes. In the AR+ group, 13 patients (59.1%) were negative, and 4 (18.2%) were positive; however, in the AR- group, 24 patients (46.1%) were negative, and 17 (32.7%) were positive (P value 0.431). The average number of lymph nodes was 1.2\u0026plusmn;2.6 in AR+ patients and 2.3\u0026plusmn;4.7 in AR- patients. In the AR+ group, 13 cases (59.1%) had zero nodes, whereas in the AR- group, 24 cases (46.1%) had zero nodes. The difference in lymph node metastasis between the two groups was not statistically significant (p value 0.268).\u003c/p\u003e\n\u003cp\u003eDCIS\u003c/p\u003e\n\u003cp\u003eDCIS was found in 35 patients (45.9%),\u0026nbsp;whereas\u0026nbsp;30 patients (40.5%) tested negative. In the AR+ group, 10 patients (45.5%) had DCIS, and 12 (54.5%) tested negative. In the AR- group, 25 patients (48.1%) tested negative, and 18 (34.6%) had DCIS. The differences between the groups were not statistically significant (p value 0.069).\u003c/p\u003e\n\u003cp\u003eNecrosis\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Necrosis was reported in samples\u0026nbsp;from\u0026nbsp;14 patients (18.9%),\u0026nbsp;whereas\u0026nbsp;34 samples did not exhibit necrosis. Within the AR+ group, necrosis was observed in 5 patients (22.7%) categorized as negative and 9 patients (40.9%) as positive. In contrast,\u0026nbsp;in\u0026nbsp;the AR- group,\u0026nbsp;necrosis\u0026nbsp;occurred\u0026nbsp;in 9 patients (17.3%), who were\u0026nbsp;negative,\u0026nbsp;and 25 patients (48.1%), who were\u0026nbsp;positive. However, this difference was not statistically significant, with a p-value of 0.808.\u003c/p\u003e\n\u003cp\u003eMicrocalcification\u003c/p\u003e\n\u003cp\u003eAmong\u0026nbsp;the total patients, 28 (35.1%) had microcalcifications,\u0026nbsp;whereas\u0026nbsp;26 (37.8%) did not. In the AR+ group, 5 patients (22.7%) were negative, and 11 (50%) were positive for microcalcifications. In the AR- group, 21 patients (40.4%) were negative, and 17 (32.7%) were positive. The differences were not statistically significant (p\u0026nbsp;value 0.273).\u003c/p\u003e\n\u003cp\u003eLymphovascular invasion\u003c/p\u003e\n\u003cp\u003eLVI invasion was present in 53 patients (71.6%) and absent in 13 patients (17.5%). In the AR+ group, it was negative in 1 patient (4.5%) and positive in 20 (91%). In the AR- group, 12 patients (23.1%)\u0026nbsp;were negative, and\u0026nbsp;33 (63.5%)\u0026nbsp;were positive. This difference was not statistically significant (p\u0026nbsp;value\u0026nbsp;of\u0026nbsp;0.055).\u003c/p\u003e\n\u003cp\u003eProliferation/mitotic rate\u003c/p\u003e\n\u003cp\u003eKi-67 expression averaged 53.3% across samples.\u0026nbsp;Among\u0026nbsp;these\u0026nbsp;samples, 4 samples (5.4%) had\u0026nbsp;percentages\u0026nbsp;of 20% or less,\u0026nbsp;whereas\u0026nbsp;47 samples (63.5%)\u0026nbsp;had percentages\u0026nbsp;above 20%. The mean Ki-67 expression was\u0026nbsp;42.5% \u0026plusmn;27.8 in the AR+ group and 57.9% \u0026plusmn;17.5 in the AR- group (p\u0026nbsp;value 0.091). In the AR+ group, 3 patients (13.6%) had Ki-67 levels of 20% or less,\u0026nbsp;whereas\u0026nbsp;1 patient (1.9%) in the AR- group\u0026nbsp;did. The difference in\u0026nbsp;the\u0026nbsp;mean\u0026nbsp;expression\u0026nbsp;between the groups was statistically significant (p\u0026nbsp;value 0.014).\u003c/p\u003e\n\u003cp\u003eLymphocyte infiltration\u003c/p\u003e\n\u003cp\u003eLymphocyte infiltration was reported to be mild in 21 samples (28.3%), moderate in 18 samples (24.3%), and severe in 5 samples (6.7%). In the AR+ group, the lymphocyte host response was reported to be mild in 9 samples (40.9%), moderate in 4 samples (18.2%), and severe in one sample (4.5%), and in the AR- group, it was reported to be low in 12 samples (23.1%), moderate in 14 samples (26.9%), and high in 4 samples (7.7%). This difference was not statistically significant (p value 0.461).\u003c/p\u003e\n\u003cp\u003eCorrelations between hematologic indices and AR\u003c/p\u003e\n\u003cp\u003eThe patients\u0026apos; mean hemoglobin and MCV indices were 13.05 and 85.8, respectively, while the average MCH value was 28.51. Forty patients (81.63%) did not have anemia, whereas nine patients (12.1%) were anemic; among them, four patients (5.4%) had microcytic anemia, four patients (5.4%) had normocytic anemia, and one patient (1.3%) had macrocytic anemia. The mean hemoglobin value for patients in the AR+ group was 13.2\u0026plusmn;1.2, whereas it was 13\u0026plusmn;1.5 in the AR- group (P-value 0.544). The mean MCV value in the AR+ group was 88.9 \u0026plusmn;5.2, and that in the AR- group was 84.5\u0026plusmn;6.9 (P-value 0.043). The mean MCH value in the AR+ group was 30.2\u0026plusmn;3.6, whereas that in the AR- group was 27.8 \u0026plusmn;3.1 (P value 0.09). In the AR+ group, nine patients (40.9%) did not have anemia, and one patient (4.5%) had macrocytic anemia. In the AR- group, 31 patients (59.6%) were not anemic, four patients (7.7%) had microcytic anemia, and four patients (7.7%) had normocytic anemia (p-value 0.03). The differences in the MCV, anemia status, and type between the two groups were statistically significant. The hematologic characteristics of patients in the AR- and AR+ groups are summarized in Table 1.\u003c/p\u003e"},{"header":"Discussion ","content":"\u003cp\u003eOverall role of AR in TNBC\u003c/p\u003e\n\u003cp\u003eAR is a type of steroid hormone nuclear receptor that plays a role in both sexes' fertility and physiological functions, especially in terms of cell cycle proliferation, by regulating DNA transcription in malignancies\u003csup\u003e[29,30]\u003c/sup\u003e. The incidence of AR ranges from 7% to over 50% in this subtype of breast cancer\u003csup\u003e[17,31,32]\u003c/sup\u003e, with various positivity cutoff points ranging from 1% to 10%\u003csup\u003e[22]\u003c/sup\u003e. Several studies conducted in recent years have revealed different aspects of the impact of the androgen receptor on the prognosis, survival, pathological response to chemotherapy, metastasis, and recurrence of TNBC patients. In this study, we explored AR status in triple-negative female patients with breast cancer and its relevance to age, clinicopathologic, and hematologic parameters.\u003c/p\u003e\n\u003cp\u003ePrevalence and selection of the cutoff point for AR positivity\u003c/p\u003e\n\u003cp\u003eCurrently, there is no standard protocol to evaluate AR positivity via IHC, so we used 1% as the cutoff, similar to many recent studies\u003csup\u003e[17,32,33]\u003c/sup\u003e. Some studies have used 5%\u003csup\u003e[34]\u003c/sup\u003e or 10%\u003csup\u003e[35–37]\u003c/sup\u003e, particularly in a few clinical studies that demonstrated the beneficial effect of anti-androgen therapy in patients with metastatic disease\u003csup\u003e[38]\u003c/sup\u003e. Additionally, this threshold is the standard for the estrogen and progesterone scoring system according to the ASCO/CAP guidelines\u003csup\u003e[39,40]\u003c/sup\u003e. Among the 74 TNBCs examined in our study, 29.7% (22:74) of the TNBC tumors expressed the AR receptor, whereas 70.3% (52:74) had quadruple-negative breast cancer. Our findings concur with the range of most research investigating AR expression via the same method and threshold\u003csup\u003e[41–43]\u003c/sup\u003e. On the other hand, the results of some studies did not align with our findings, with higher and lower rates of positivity ranging from 13% to 63%\u003csup\u003e[17,19,26,44,45]\u003c/sup\u003e. These wide ranges of differing findings suggest that a probable factor influencing AR expression in TNBC worldwide is the diversity in demographic, racial, and ethnic characteristics of the target population\u003csup\u003e[26]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAssociations between AR and patient characteristics\u003c/p\u003e\n\u003cp\u003eOur study found a mean diagnosis age of 48.7 years, with AR+ (51 years) older than AR- (47.8 years) patients, but not statistically significant. This differs from Dubrava et al., who reported significant age differences (47–69 years) in 137 TNBC samples at a 10% AR cutoff. A Japanese study demonstrated a positive relationship between older age and lower recurrence rate in AR+ TNBC patients\u003csup\u003e[45]\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRelationships of AR with clinicopathologic parameters\u003c/p\u003e\n\u003cp\u003eNo significant differences in clinicopathologic features (tumor size, lymphocytic infiltration, lymph node invasion, microcalcification, necrosis, tumor grade, tumor type, DCIS, LVI) were found between AR+ and AR- groups. However, DCIS and LVI showed non-significant but meaningful trend (p=0.055, p=0.066, 0.05\u0026lt;p\u0026lt;0.1), with higher LVI (95% vs. 73%) and DCIS (54% vs. 41%) in AR+ vs. AR- tissues. Larger samples may yield significance. Overall, explorations emphasize the poor prognostic effect of LVI on overall survival (OS) and disease-free survival (DFS) in TNBC patients\u003csup\u003e[44,46,47]\u003c/sup\u003e. Merckx et al. reported higher DCIS in AR+ patients with variable relapse effects\u003csup\u003e[48]\u003c/sup\u003e. Conversely, American studies found an inverse DCIS-AR link in TNBC\u003csup\u003e[36,45]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAR’s prognostic role in TNBC varies. A meta-analysis of 2826 cases linked AR positivity to better DFS, not OS\u003csup\u003e[17,22]\u003c/sup\u003e. A 2021 study between 75 TNBC patients found AR as an independent predictor of better outcomes, especially in older patients. Adamo et al. reported poorer OS and DFS in AR- patients (n=121), tying low AR to metastasis\u003csup\u003e[42,49]\u003c/sup\u003e. Some studies linked AR+ to similar outcomes, such as a 2024 study that found no AR-prognosis link in TNBC, reflecting varied findings across nationalities.\u003csup\u003e[26]\u003c/sup\u003e. AR’s prognostic role in TNBC remains debated.\u003c/p\u003e\n\u003cp\u003eAR and Proliferation Rate Indicator Correlations\u003c/p\u003e\n\u003cp\u003eIn our study, the mean Ki-67 index was 55.4% (AR-/AR+, 57.9:42.5) in all TNBC tumors. Our results revealed a trend toward lower mitotic scores in the AR+ group than in the AR- group at a cutoff of 20%, with a statistically significant difference (p value 0.014). This finding aligns with the majority of research in this field; for example, Dicei and colleagues, along with Leone et al., reported that TNBC patient tumors expressing AR exhibited a lower mitotic rate\u003csup\u003e[19,43]\u003c/sup\u003e. The prognostic role of Ki-67 has been investigated and identified as a valuable marker; a study on TNBCs in 2017 revealed that Ki-67 expression above 20% was significantly associated with poor outcomes\u003csup\u003e[49]\u003c/sup\u003e and A study involving 1800 patients in China showed that Ki-67 could serve as a prognostic indicator beyond a 30% cutoff, correlating with worse OS and DFS, and highlighted that patients treated with adjuvant chemotherapy had longer OS than those with low Ki-67\u003csup\u003e[50]\u003c/sup\u003e, and the same result was reported for a 40% cutoff in meta-analysis research, which included 35 studies with 7716 enrolled patients\u003csup\u003e[51]\u003c/sup\u003e. Furthermore, an exploration of clinicopathologic evaluations by Urru and colleagues revealed a significant increase in the mortality rate associated with Ki-67 greater than 16% in triple-negative breast cancers\u003csup\u003e[52]\u003c/sup\u003e. On the other hand, some studies exploring Ki-67 as a prognostic marker did not find significant differences between AR+ and AR- patients at a 50% threshold. Nevertheless, there appears to be an inverse correlation between Ki-67 and AR positivity, which has been reported in most of the studies.\u003c/p\u003e\n\u003cp\u003eAR and Hematologic Index associations\u003c/p\u003e\n\u003cp\u003eThe microcytic anemia was present in both groups, with statistically significant findings. Notably, the mean hemoglobin level and mean MCV were greater in the AR-positive group. Various factors, including chemotherapy complications, tumor-induced bleeding, and chronic inflammatory conditions, can cause anemia in TNBC patients. While few studies have been conducted on this topic, hemoglobin levels are generally low in patients with breast cancer\u003csup\u003e[53,54]\u003c/sup\u003e. However, the incidental finding of increased mean hemoglobin and MCV in the AR-positive group provides an opportunity to clarify hypotheses related to this phenomenon. Androgens, particularly testosterone, influence erythropoiesis by stimulating erythropoietin activity and enhancing red blood cell production\u003csup\u003e[53]\u003c/sup\u003e. Additionally, androgens may directly affect hematopoietic stem cells within the bone marrow, promoting erythrocyte production. Previous studies have demonstrated the beneficial effects of androgens in treating anemia in patients with aplastic anemia and other bone marrow failure disorders\u003csup\u003e[55,56]\u003c/sup\u003e. Specifically, research focusing on women with congenital adrenal hyperplasia has shown that androgens can positively impact hemoglobin and hematocrit (Hct) levels\u003csup\u003e[57]\u003c/sup\u003e. Examining the trajectory of testosterone in cancer treatment reveals significant findings. In prostate cancer patients receiving androgen deprivation therapy, which is often facilitated by agents such as abiraterone acetate, anemia is a notable side effect. These results can be explained by the above mechanisms\u003csup\u003e[58]\u003c/sup\u003e. Therefore, while hormonal therapies are not a treatment option for TNBC patients, as they are for other subtypes, the effects of androgen receptor presence can be explained through its potential to stimulate erythropoiesis and influence bone marrow function. Given that no prior studies have investigated this specific issue and that our findings emerged accidentally, further systematic research is needed to validate these hypotheses.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur findings demonstrated that approximately 29% of TNBC patients expressed AR, and a statistically significant relationship was found between Ki67, a proliferative index of the tumor, and AR, MCV, and Hemoglobin. We found no associations with clinicopathologic or demographic characteristics; however, there were meaningful but insignificant results regarding DCIS and LVI. Our findings align with previous studies and lay the groundwork for future research. These results emphasize the importance of AR expression in managing TNBC. AR status could aid in developing personalized treatment strategies, distinguishing between AR-positive and AR-negative TNBC. We recommend conducting further clinical evaluations with a larger sample size and implementing a prediction model for AR to clarify its prognostic role in TNBC and improve therapeutic options. We hope our survey aids in addressing challenges in this field.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, the sample size from 2017 to 2023 was inadequate for accurate prevalence estimation, which may affect the generalizability of our findings. Additionally, relying on medical records for clinicopathological data can introduce biases due to varying quality of information. While IHC is a common method for assessing AR expression, differences in staining techniques may impact the consistency of results.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are thankful to Mrs. Rashidi at the Kerman Pathology Research Center for her support in conducting the IHC method and to Dr. Rezaie for performing the statistical analysis of our findings. Additionally, we extend our appreciation to all individuals who contributed to this research, including those who helped with sample collection, provided kits, and offered scientific guidance throughout the writing of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAliasghar Tirgar was involved in the design, coordination, and conceptualization of the study, as well as sample collection, data interpretation, and manuscript drafting. Yasamin Zamanian, Yasaman Mousavi, and Fatemeh Khodadadpour Mahani contributed to sample collection, interpretation of the findings, and drafting of the manuscript. Fatemeh Fathi and Fatemeh Nakhaie participated in sample collection. Vahid Moazed, Mohammad Khaksari, and Elham Jafari provided expert supervision in their respective fields of medical oncology, physiology, and pathology. All authors reviewed and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding sources\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by grants from the Kerman University of Medical Sciences, Kerman, Iran (Grant No. 400000061).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed in the present study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe hereby give our consent for the publication of the manuscript, along with all accompanying images and data that may disclose our identities. We understand that this information will be publicly accessible online and may be reproduced in accordance with the terms established by Discover Oncology, which could affect our privacy. We have reviewed the manuscript before publication and acknowledge that it won't be possible to remove it from the record except under extraordinary circumstances.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors do not have any competing financial/non-financial interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eand consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research followed the principles outlined in the Declaration of Helsinki and received approval from the Ethics Committee of Kerman University of Medical Sciences (Ethics code: IR.KMU.AH.REC.1400.191). The requirement for informed consent was waived by the ethics committee/IRB of Kerman University of Medical Sciences due to the retrospective nature of the study and the de-identification of patient information.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eElengoe A. A Short Review on Breast Cancer. Int J Biotechnol Biomed 2024;1(1):1\u0026ndash;11. \u003c/li\u003e\n\u003cli\u003eLee KL, Kuo YC, Ho YS, Huang YH. Triple-negative breast cancer: current understanding and future therapeutic breakthrough targeting cancer stemness. Cancers (Basel) 2019;11(9):1334. \u003c/li\u003e\n\u003cli\u003eda Silva JL, Nunes NCC, Izetti P, de Mesquita GG, de Melo AC. Triple negative breast cancer: A thorough review of biomarkers. Crit Rev Oncol Hematol 2020;145:102855. \u003c/li\u003e\n\u003cli\u003eEngebraaten O, Vollan HKM, B\u0026oslash;rresen-Dale AL. Triple-negative breast cancer and the need for new therapeutic targets. 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Available from: https://doi.org/10.1158/1538-7445.SABCS23-PO5-03-10\u003c/li\u003e\n\u003cli\u003eAdamo B, Ricciardi GRR, Ieni A, Franchina T, Fazzari C, San\u0026ograve; MV, et al. The prognostic significance of combined androgen receptor, E-Cadherin, Ki67 and CK5/6 expression in patients with triple negative breast cancer. Oncotarget 2017;8(44):76974. \u003c/li\u003e\n\u003cli\u003eZhu X, Chen L, Huang B, Wang Y, Ji L, Wu J, et al. The prognostic and predictive potential of Ki-67 in triple-negative breast cancer. Sci Rep 2020;10(1):225. \u003c/li\u003e\n\u003cli\u003eWu Q, Ma G, Deng Y, Luo W, Zhao Y, Li W, et al. Prognostic value of Ki-67 in patients with resected triple-negative breast cancer: a meta-analysis. Front Oncol 2019;9:1068. \u003c/li\u003e\n\u003cli\u003eUrru SAM, Gallus S, Bosetti C, Moi T, Medda R, Sollai E, et al. Clinical and pathological factors influencing survival in a large cohort of triple-negative breast cancer patients. BMC Cancer 2018;18(1):56. \u003c/li\u003e\n\u003cli\u003eWarren AM, Grossmann M. Haematological actions of androgens. Best Pract Res Clin Endocrinol Metab 2022;36(5):101653. \u003c/li\u003e\n\u003cli\u003eSharma P, Georgy JT, Andrews AG, John AO, Joel A, Chacko RT, et al. Anemia requiring transfusion in breast cancer patients on dose-dense chemotherapy: Prevalence, risk factors, cost and effect on disease outcome. Support Care Cancer 2022;30(6):5519\u0026ndash;26. \u003c/li\u003e\n\u003cli\u003eNassani M, Fakih R El, Passweg J, Cesaro S, Alzahrani H, Alahmari A, et al. The role of androgen therapy in acquired aplastic anemia and other bone marrow failure syndromes. Front Oncol 2023;13:1135160. \u003c/li\u003e\n\u003cli\u003ePagliuca S, Kulasekararaj AG, Eikema DJ, Piepenbroek B, Iftikhar R, Satti TM, et al. Current use of androgens in bone marrow failure disorders: a report from the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation. Haematologica 2023;109(3):765. \u003c/li\u003e\n\u003cli\u003eKarunasena N, Han TS, Mallappa A, Elman M, Merke DP, Ross RJM, et al. Androgens correlate with increased erythropoiesis in women with congenital adrenal hyperplasia. Clin Endocrinol (Oxf) 2017;86(1):19\u0026ndash;25. \u003c/li\u003e\n\u003cli\u003eGrossmann M, Zajac JD. Hematological changes during androgen deprivation therapy. Asian J Androl 2012;14(2):187. \u003c/li\u003e\n\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":"Triple negative Breast cancer, Androgen receptor, Clinicopathology, Hematology","lastPublishedDoi":"10.21203/rs.3.rs-7771474/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7771474/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eTriple-negative breast cancer (TNBC) is an aggressive subtype with significant treatment challenges. Emerging evidence suggests that the androgen receptor (AR) may play a key role in prognosis, but findings are inconsistent. This study aimed to clarify the relationship between AR status and TNBC while examining associated clinicopathologic, hematologic, and demographic factors.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe analyzed AR staining in 74 TNBC cases from 250 tissue samples collected from 2017 to 2023. Patient age, tumor size, lymphovascular invasion, Ki-67 levels, and hematologic indices like mean corpuscular volume (MCV) and hemoglobin (Hb) were evaluated between AR-positive and AR-negative groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eOf tumors analyzed, 29.8% (22 out of 74) were AR-positive. These tumors were generally smaller, had lower Ki-67 rates, and were more common in older women. AR expression correlated significantly with MCV (p\u0026thinsp;=\u0026thinsp;0.043) and Ki-67 (p\u0026thinsp;=\u0026thinsp;0.014), and showed non-significant positive associations with ductal carcinoma in situ (DCIS) (p\u0026thinsp;=\u0026thinsp;0.069) and lymphovascular invasion (LVI) (p\u0026thinsp;=\u0026thinsp;0.055).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eOur findings suggest that AR may be a useful biomarker in TNBC progression, underscoring the need for further research to assess its potential as a targeted therapeutic marker to improve treatment strategies and patient outcomes.\u003c/p\u003e","manuscriptTitle":"Assessing the Androgen Receptor Status in Clinicopathologic and Hematologic Characteristics of the Triple-negative Breast Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-13 08:15:13","doi":"10.21203/rs.3.rs-7771474/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":"2e502181-7e6b-4a0d-a240-32924000edf2","owner":[],"postedDate":"November 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-07T09:39:48+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-13 08:15:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7771474","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7771474","identity":"rs-7771474","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}