Clinicopathological Features and Prognostic Implications of HER2-Low in Early-Stage Male Breast Cancer: A Retrospective Analysis

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Current knowledge suggests that low HER2 expression could be identified as a special entity for treatment. However, research on HER2-low in early-stage male breast cancer remain limited. Methods: This retrospective study screened male BC patients at a single institution between January 2010 and September 2023. Early-stage cases with non-HER2-positive tumors were included and categorized into HER2-low and HER2-zero groups. Clinicopathological features were collected and compared between the two groups. The primary endpoints were disease-free survival (DFS) and overall survival (OS). Statistical analysis was conducted viadescriptive statistics, the Kaplan‒Meier method with the log-rank test, and the Cox proportional hazards model to evaluate differences in DFS and OS between the groups. Results: In 99 early-stage non-HER2-positive male BC patients, 41 were classified as HER2-low, and 58 were classified as HER2-zero. In terms of clinicopathological features, the HER2-low subgroup exhibited higher androgen receptor (AR) expression (P=0.003). In terms of survival, no significant difference was observed in DFS (P=0.1), but the HER2-low subgroup had a significantly longer OS than the HER2-zero subgroup (P=0.01). Multivariate analysis revealed that age and TNM stage wereindependent prognostic factors for DFS, whereas age and HER2-low status were independent prognostic factors for OS. Conclusion: In early-stage male BC, the HER2-low population differed in clinicopathological features and prognostic role compared to HER2-zero counterparts. Compared with the HER2-zero subgroup, the HER2-low subgroup had a better OS, and HER2-low status was determined to be an independent prognostic factor for OS but not for DFS. Male breast cancer HER2-low HER2-zero Clinicopathologic features Prognosis Figures Figure 1 Figure 2 Introduction Male breast cancer is a rare disease accounting for less than 1% of all breast cancer cases(1), with its incidence gradually increasing(2). Owing to the rarity and lack of large-scale studies on male BC, current treatments are predominantly derived from those established for female BC. Research indicates that there are significant differences in the clinicopathological characteristics and survival outcomes between male and female patients with BC(1), underscoring the necessity for a deeper understanding of male BC. Breast cancer subtypes are categorized on the basis of the status of hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2). Traditionally, breast cancers are classified as either HER2-positive or HER2-negative(3). For HER2-negative tumors, it was previously believed that these patients could not benefit from anti-HER2 treatments(4). However, with the advent of new drugs, a subset of HER2-negative cancers with low levels of HER2 expression, termed HER2-low, has shown a response to anti-HER2 antibody‒drug conjugates (ADCs), such as T-DXd(5). This advancement has changed the traditional binary classification of HER2 status. Currently, HER2-low breast cancer has been the focus of extensive research. This subtype represents a substantial portion, potentially accounting for up to half of all breast cancer cases(6). Compared to their HER2-zero counterparts, HER2-low tumors exhibit higher rates of HR positivity and different responses to treatment(7). A meta-analysis of 23 retrospective studies indicated that patients with HER2-low breast cancer have better DFS and OS in the early stage(6). However, research specifically on HER2-low male BC is limited. To date, only six studies have focused on or included this population, reporting that the proportion of HER2-low cases varies between 21% and 73%(8–13). The specific characteristics and survival outcomes of HER2-low male BC remain underexplored. This comparative analysis aimed to determine whether HER2-low early-stage male BC represents a distinct clinical entity with unique prognostic implications. Methods Patient Selection and Data Collection This retrospective study reviewed patients who were diagnosed with breast cancer and hospitalized at our institution between January 2010 and September 2023. Among these patients, only male patients were included. Further exclusions were made on the basis of the following criteria: patients with advanced disease, HER2-positive or unknown HER2 status, intraductal carcinoma, unavailable medical records, and non-primary breast cancer. The enrolled patients were classified into two groups based on HER2 expression: HER2-zero and HER2-low. We extracted baseline clinicopathological features from the patients’ electronic medical records. These features included age at diagnosis, family history of cancer, body mass index (BMI), comorbidities, tumor grade, TNM stage, estrogen receptor (ER) status, progesterone receptor (PR) status, AR status, Ki-67 index, and treatment modalities (including surgery, radiotherapy, and adjuvant chemotherapy). Survival status was determined through follow-up calls. Definition of Variables HER2 expression was assessed via immunohistochemistry (IHC) and categorized as follows: IHC 0, IHC 1+, IHC 2+, and IHC 3+. For patients with HER2 IHC 2 + tumors, in situ hybridization (ISH) was conducted. Cases with an IHC score of 0 were defined as HER2-zero, whereas cases with an IHC score of 1 + or an IHC score of 2+/ISH negative were defined as HER2-low. Tumor staging followed the American Joint Committee on Cancer (AJCC) staging system, seventh edition. ER and PR were considered positive if they exceeded 1%. HR status was deemed positive with ER and/or PR positivity and negative with both ER and PR negativity. The AR status was positive if it exceeded 10%. A high Ki-67 index was defined as greater than 20%. DFS was the interval from the completion of primary treatment to recurrence, distant metastasis, or death. OS was defined as the time from breast cancer diagnosis to death from any cause or the latest follow-up. Statistical Analysis Clinicopathological features were summarized via descriptive statistics. Continuous variables were reported as means or medians, and categorical variables were reported as frequencies and percentages. We compared variable distributions between the HER2-zero and HER2-low groups via chi-square or Fisher’s exact tests for categorical variables and the Mann‒Whitney test for continuous variables. Survival probabilities were estimated via the Kaplan‒Meier method, with intergroup comparisons performed via log-rank tests. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors for DFS and OS. The results were expressed as hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Variables with P values < 0.1 in the univariate analysis were included in the multivariate analysis. A P value < 0.05 was considered to indicate statistical significance. Statistical analyses were conducted via SPSS version 23.0 (SPSS Inc., Chicago, IL, USA) and R Studio software, version 4.1.1. Results Baseline Clinicopathological Characteristics After screening 38,632 breast cancer patients, we identified 133 male patients, accounting for 0.34% of all BC patients. Among these patients, 99 patients with non-HER2-positive tumors were included in the final analysis. These patients were further divided into two subgroups: 41 patients in the HER2-zero group and 58 patients in the HER2-low subgroup. The detailed screening process is illustrated in Fig. 1 . The baseline characteristics of the two subgroups are presented in Table 1 . Table 1. Comparative analysis of baseline characteristics between the HER2-zero and HER2-low subgroup Characteristics HER2-zero (n = 41) HER2-low (n = 58) p value No. Percentage (%) No. Percentage (%) Age at diagnosis Mean (Range) 57 (34–84) 59 (32–81) 0.619 ≤ 35 2 4.88 2 3.45 0.664 35–65 27 65.85 34 58.62 ≥ 65 12 29.27 22 37.93 Family history of cancer Yes 15 36.59 19 32.76 0.830 No 26 63.41 39 67.24 BMI Average 25.88 25.42 0.563 Mean (Range) 25.46 (18.44–34.42) 24.51 (18.34–37.42) 0.471 BMI > = 24 25 60.98 33 57.89 0.836 BMI < 24 16 39.02 24 42.11 Grade Grade I 3 7.32 5 8.62 0.879 Grade II 25 60.98 36 62.07 Grade III 3 7.32 6 10.34 Unknown 10 24.39 11 18.97 T stage T0-T2 29 85.29 49 92.45 0.473 T3-T4 5 14.71 4 7.55 N stage N0-N1 31 75.61 48 84.21 0.311 N2-N3 10 24.39 9 15.79 TNM stage 0-II 23 67.65 43 81.13 0.200 III 11 32.35 10 18.87 ER status (> 1%) Positive 38 92.68 54 93.10 1.000 Negative 3 7.32 4 6.90 PR status (> 1%) Positive 38 92.68 52 89.66 0.732 Negative 5 7.32 6 10.34 HR status (> 1%) Positive 39 95.12 55 94.83 1.000 Negative 2 4.88 3 5.17 AR status (> 10%) Positive 9 21.95 30 51.72 0.003 Negative 1 2.44 3 5.17 Unknown 31 75.61 25 43.10 Ki-67 index (> 20%) Positive 18 43.90 26 44.83 1.000 Negative 21 51.22 30 51.72 Unknown 2 4.88 2 3.45 Subtype Luminal A 15 36.59 19 32.76 0.896 Luminal B 24 58.54 35 60.34 Triple-negative 2 4.88 4 6.90 Surgery Total mastectomy 9 21.95 22 37.93 0.222 Modified radical mastectomy 27 65.85 32 55.17 Others 5 12.2 4 6.90 Adjuvant Radiotherapy Yes 14 34.15 11 18.97 0.165 No 23 56.10 43 74.14 Unknown 4 9.76 4 6.90 Adjuvant Chemotherapy Yes 27 65.85 29 50.00 0.151 No 14 34.15 29 50.00 Chemotherapy Regimens a Taxane involved 18 66.67 19 65.52 0.499 Anthracycline involved 20 74.07 14 48.28 0.207 Platinum-based 0 0 2 6.90 0.224 Comorbidities Hypertension 12 29.27 17 29.31 1.000 Diabetes mellitus 10 24.39 9 15.52 0.307 Hepatic disease c 6 14.63 5 8.62 0.518 Coronary artery disease 3 7.32 3 5.17 0.690 Cerebrovascular disease 1 2.44 2 3.45 1.000 Malignant tumors of other types 3 7.32 4 6.90 1.000 *Abbreviations: ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; AR, androgen receptor; BMI, body mass index. *Remarks: P values in bold indicate statistically significant results. a Chemotherapy regimens may overlap with each other. b Metastatic organs may overlap with each other. c Hepatic disease includes fatty liver disease, viral hepatitis, and liver cirrhosis. No significant differences were observed between the two groups in terms of ER, PR, HR, or Ki-67 expression. However, the HER2-low group exhibited significantly higher AR expression (P = 0.003). Other clinicopathological characteristics, including stage, BMI, treatment modality, and comorbidities, were similar between the two subgroups. Survival Outcomes and Cox Regression Analysis The median follow-up time for this study was 70 months. The analysis of DFS between the two subgroups did not reveal a statistically significant difference, although the median DFS in the HER2-low subgroup tended to be longer than that in the HER2-zero subgroup (not reached vs. 106 months, P = 0.1). In terms of OS, the HER2-low subgroup had a significantly longer median OS than the HER2-zero subgroup (not reached vs. 121 months, P = 0.01). The results of the survival analysis are illustrated in Figs. 2 a and 2 b. Univariate and multivariate Cox regression analyses were performed, and the results are summarized in Table 2 . Age, TNM stage, and endocrine therapy were included in further multivariate analysis for DFS, in which younger age (P = 0.025) and TNM stage (P = 0.047) were significant prognostic factors. The multivariate analysis of OS included age, TNM stage, HR status, and HER2 status, with HER2-low status (P = 0.050) and younger age (P = 0.026) being significant prognostic factors for better OS. Table 2 Univariate and multivariate analyses of variables correlated with DFS and OS in HER2-zero and HER2-low patients Variables Univariate Analysis Multivariate Analysis DFS OS DFS OS Hazard Ratio (95% CI) p Value Hazard Ratio (95% CI) p Value Hazard Ratio (95% CI) p Value Hazard Ratio (95% CI) p Value Age, Years >=55 Reference Reference Reference =60 Reference Reference Reference < 60 0.48 (0.23-1.00) 0.05 0.34 (0.14–0.83) 0.018 0.33 (0.13–0.88) 0.026 Comorbidities Yes Reference Reference No 1.01 (0.48–2.09) 0.987 1.14 (0.48–2.69) 0.766 Family history of cancer Yes Reference Reference No 0.93 (0.42–2.05) 0.860 0.89 (0.34–2.33) 0.808 Family history of breast cancer Yes Reference Reference No 0.96 (0.23–4.05) 0.950 1.15 (0.15–8.72) 0.893 Body Mass Index (BMI) >=24.0 Reference Reference < 24 0.99 (0.47–2.09) 0.970 0.75 (0.30–1.88) 0.538 T stage T3-T4 Reference Reference T0-T2 0.43 (0.16–1.14) 0.090 0.40 (0.13–1.22) 0.107 N stage N2-N3 Reference Reference N0-N1 0.58 (0.25–1.31) 0.189 0.49 (0.18–1.32) 0.158 TNM stage III Reference Reference Reference Reference I-II 0.51 (0.24–1.13) 0.096 0.36 (0.14–0.93) 0.035 0.45 (0.20–0.99) 0.047 0.58 (0.20–1.66) 0.307 ER status positive Reference Reference negative 1.73 (0.52–5.77) 0.374 2.01 (0.46–8.87) 0.357 PR status positive Reference Reference negative 2.40 (0.82–6.99) 0.110 4.12 (1.31–12.99) 0.016 HR status positive Reference Reference Reference negative 2.00 (0.47–8.52) 0.348 3.83 (0.85–17.23) 0.08 1.81 (0.37–8.94) 0.469 HER2 status HER2-low Reference Reference Reference HER2-0 1.86 (0.87–3.94) 0.107 3.04 (1.20–7.67) 0.019 2.83 (1.00-7.98) 0.050 Subtype Luminal A Reference 0.333 Reference 0.234 Luminal B 1.82 (0.77–4.32) 0.174 1.42 (0.50–4.02) 0.509 Triple-negative 2.41 (0.49–11.70) 0.277 4.27 (0.80-22.73) 0.089 Radiotherapy Yes Reference Reference No 0.60 (0.26–1.37) 0.224 0.59 (0.19–1.81) 0.354 Adjuvant chemotherapy Yes Reference Reference No 1.05 (0.50–2.19) 0.907 1.00 (0.41–2.43) 0.997 Endocrine therapy Yes Reference Reference Reference No 2.17 (1.00-4.71) 0.051 3.08 (1.29–7.35) 0.012 1.70 (0.75–3.84) 0.202 Discussion In recent years, low HER2 expression has been a research focus in breast cancer. A variety of conclusions have been drawn from research on HER2-low female BC, but the issue has not been studied sufficiently in male patients. Our study investigated the factors related to the prognosis of male BC and focused on the characteristics of HER2-low male BC. Age was an independent predictor for both DFS and OS in our male BC population. To our knowledge, younger age is a factor for poor prognosis in female BC(14). The association between younger age and poor prognosis in women is largely due to the pathogenic effect of estrogen before menopause. Natural menopause exempts later-diagnosed breast tumors from hormonal stimulation, thus decreasing the risk of recurrence and death. In contrast, other studies, including ours, suggest that older age is a risk factor for OS in male patients(15–17). The different correlations between age and survival in male patients are likely due to the lack of age-dependent endocrine changes, as in female BC patients(18). The lower survival rates in older male BC patients, which resemble other tumor types, can also be attributed to the increase in mortality from other chronic diseases and decreased tolerance to anti-tumor therapy with aging(19). Apart from age, our finding of TNM stage indicating better survival corresponds with other retrospective studies. However, other reported characteristics, including the ER/PR status, histological grade, and triple-negative subtype, were not significant(16, 17, 20–22). As reported, radical mastectomy, chemotherapy, radiotherapy, and endocrine therapy were associated with better OS, and radical mastectomy and endocrine therapy were associated with better DFS in male BC(23, 24), which was not observed in our study. Most studies did not distinguish the stage of disease, and in a study on early-stage male BC, PR positivity, chemotherapy, radiotherapy, and endocrine therapy were associated with better OS(23). We focused on the HER2-low population in male BC. According to the literature, the incidence of HER2-low BC varies with different HR statuses in females. The incidence of HER2-low BC is 45–65%(25–27) in females and 35–72% (8, 10–12) in males; in this study, the incidence of HER2-low BC was 48%. Among HR-positive female BC patients, HER2-low cases account for 60–90%(4, 26, 28–30), which is often higher than in HR-negative female BC patients(25, 26, 28). However, this conclusion does not seem to be as solid in males with BC. According to a retrospective study from the Korean Breast Cancer Society, the proportions of HER2-low patients were 33.6% and 23% in the HR-positive and HR-negative subgroups, respectively (P < 0.001)(13). In contrast, the incidence of HER2-low in HR-positive and HR-negative male BC in this study was 52.9% and 42.9% (p = 0.30), respectively, without a significant disparity. Other studies are not considered due to inconclusive results. This indefiniteness is probably due to the higher incidence of HR positivity in male BC. The percentage of HR-positive males with BC was 93.7% in this study and 89–99%(8, 10, 31, 32) in existing studies, which is significantly higher than the percentage of 60–70% in females with BC. A study revealed that ERα clustered with PR and its isoforms in female BC, whereas ERα clustered with ERβ and AR in male BC(33), which could partially explain the increased HR expression in male BC. However, the role of ERβ has not been fully elucidated in both female and male BC patients and is possibly regulated by 3′-untranslated regions (UTRs)(34) and microRNAs(35). As the disparity in HR expression between the two subgroups in this study was not statistically significant, we did not distinguish different HR statuses in subsequent analyses. The correlation between AR expression and prognosis differs among BC subtypes. Retrospective studies have shown that a higher AR is associated with improved outcomes in ER+/HER2- female BC patients but with worse outcomes in HER2 + patients(36, 37). Androgen receptor inhibitors of different mechanisms also act differently among subtypes. In female BC, second-generation androgen receptor antagonists have shown efficacy in triple-negative BC (38) but not in HR-positive BC(39). In contrast, evidence from a clinical trial demonstrated the efficacy of nonsteroidal selective androgen receptor modulators (SARMs) in HR-positive/HER2-negative female BC patients(40). Such varied roles of AR in different BC subtypes may be the result of potential complex crosstalk among the ER, AR, and HER2 pathways(25). In male BC patients, the incidence of AR positivity is 34–95%(41, 42). Our study revealed greater AR expression in the HER2-low subgroup than in the HER2-zero subgroup, which has not yet been investigated in previous studies. A clinical trial featuring SARMs in HR+/HER2- metastatic male BC revealed a correlation between AR status and positive treatment outcomes(43). As HER2-low male BC patients have higher AR expression, SARMs may be a potential option for HR+/HER2-low male BC in the metastatic stage. However, as AR expression is not included in every IHC test, only 57% of the patients had a known AR status. More evidence is needed to confirm whether a definite correlation lies between the AR and HER2 pathways and whether AR expression holds a predictive value in the treatment of male BC in later stages. In addition to those mentioned above, other clinicopathological features were investigated. However, unlike disparities in HER2-low female BC, other features, such as the age at diagnosis and lymph node involvement, were found to be consistent in this study. The relationship between HER2-low status and survival in female BC has been controversial. Earlier studies on 9,872 and 1,150 early-stage female BC patients suggested that HER2-low patients have a worse prognosis than HER2-zero patients do. Two studies in our center on early-stage and metastatic female BC reported improved OS and 5-year DFS in HR-positive/HER2-low female BC (44, 45). Research in other institutions has reached similar conclusions regarding early-stage female BC(7, 13, 46), particularly in women with high genomic risk(47). The role of HER2-low status as a prognostic factor has also been controversial in previous studies on female BC. Some studies support the role of HER2-low status as a positive indicator of OS and/or DFS(48–50); some studies have reached opposite conclusions(51, 52), whereas others have concluded that HER2-low status is irrelevant to survival(27, 53). With a median follow-up of 70 months, the HER2-low group in our study had a significantly longer OS compared to the HER2-zero group in the survival analysis. A tendency for longer DFS was also observed, although the difference was not significant. Accordingly, HER2-low status was also proven to be a dependent prognostic factor for better OS. However, recent studies on early-stage male BC have failed to prove a definite correlation between HER2-low status and survival. A recent study on 120 early-stage male BC patients from 1995–2022 reported a tendency toward better survival in patients with HER2-zero BC, but the correlation was not statistically significant(9). Although the size of our sample is not as large, our population was screened from a relatively recent period and belongs to a different race. These factors may result in discrepant levels of pathological diagnosis and diverse genetic features, leading to different conclusions. Another study of 5235 early-stage BC patients reached an insignificant conclusion, but as male patients accounted for only 1.2% and 0.4% of the HER2-low and HER2-zero subgroup, respectively(54), and a subgroup analysis was not carried out in male patients, the conclusion of this study may not be generalizable to male BC patients. Only one study in male BC patients evaluated the prognostic role of HER2-low status via Cox regression analysis, and the results were not significant; however, the study population included only metastatic male BC patients(12). We attempted to analyse the possible reasons for our findings concerning HER2-low status and survival. Considering the higher HR expression in male BC, the cross-talk between HR and HER2 is likely to contribute to the better prognosis of HER2-low male BC(55). Another contributing factor is the dynamic nature of HER2 expression, including intratumoral heterogeneity, laboratory error, and the alteration of HER2 expression in primary and metastatic sites [34][35]. Future investigations on HER2-low patients should also consider these factors, and repeated biopsies should be performed if necessary. Given that this issue has rarely been investigated in male BC, our findings suggest that HER2-low male BC is unique in terms of prognosis in both male and female BC. Newly emerged ADCs have demonstrated efficacy in HER2-low female BC(56–59). In the DESTINY-Breast04 trial, the novel ADC T-DXd showed efficacy over standard chemotherapy in HER2-low advanced BC(5), expanding the scope of the application of novel ADC drugs in HER2-low breast cancer. However, the recently published D-B04 trial included only two men out of 557 randomized patients, and only one male patient participated in the DAISY trial(60). Given that male patients are rarely included in clinical trials and are insufficiently investigated in retrospective studies, our study provides supplements and updates to the research on HER2-low in male BC patients. To our knowledge, our study is the first to report a positive result in the prognostic role of HER2-low male BC in the Chinese population. Our findings on HER2-low male BC indicate that it is a unique entity in early-stage male BC, and the stratification of HER2 may be beneficial for refining treatment modalities for male BC. The distinctiveness of HER2-low BC also provides insight into novel treatment options for HER2-low male BC in the later metastatic stage, which is expected to be a promising topic for future research. Limitations of this study include its retrospective nature, insufficient sample size, reliance on a single-center approach, incomplete patient information, and partial loss to follow-up. Conclusion Our study focused on the features of HER2-low early-stage male BC in a single institution. A significant difference in AR positivity was found, in favour of the HER2-low subgroup. Compared with the HER2-0 subgroup, the HER2-low subgroup had a better OS, and HER2-low status was determined to be an independent prognostic factor for OS but not for DFS. Abbreviations BC Breast Cancer DFS Disease-Free Survival OS Overall Survival AR Androgen Receptor HR Hormone Receptor ER Estrogen Receptor PR Progesterone Receptor HER2 Human Epidermal Growth Factor Receptor 2 ADCs Anti-HER2 Antibody‒Drug Conjugates BMI Body Mass Index IHC Immunohistochemistry ISH In Situ Hybridization AJCC American Joint Committee on Cancer HR Hazard Ratio CI Confidence Interval UTRs Untranslated Regions SARMs Selective Androgen Receptor Modulators Declarations Ethics approval and consent to participate This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. This study received approval from the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS), and all participants provided written informed consent. Consent for publication Not Applicable. Availability of data and materials The datasets generated and analysed during the current study are not publicly available due to patient privacy, but are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding The study was supported by the CAMS Innovation Fund for Medical Sciences (CIFMS, 2021-I2M-1-014). Authors' contributions Qiang Sa, Hangcheng Xu and Jiayu Wang designed the study. Qiang Sa and Hangcheng Xu did the literature search and wrote the manuscript. Yan Wang, Yiran Zhou and Yun Wu were responsible in data acquisition. Qiang Sa, Hangcheng Xu and Yan Wang analyzed and interpreted the study results. Jiayu Wang and Peng Yuan revised the manuscript. 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Male breast cancer in the United States: Treatment patterns and prognostic factors in the 21st century. Cancer. 2020;126(1):26-36. Zhao J, Wang B, Zhao J, Mao Y, Liu J, Yang Y. Male breast cancer: A closer look at patient and tumor characteristics and factors associated with survival. Thorac Cancer. 2020;11(11):3107-16. Wu Q, Yang F, Liu Y, Zhang H, Zhang S, Xin L, et al. Analysis of clinicopathological characteristics and prognostic factors of early-stage human epidermal growth factor receptor 2 (HER2)-low breast cancer: Compared with HER2-0 breast cancer. Cancer Med. 2023;12(19):19560-75. Schettini F, Chic N, Brasó-Maristany F, Paré L, Pascual T, Conte B, et al. Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer. NPJ Breast Cancer. 2021;7(1):1. Horisawa N, Adachi Y, Takatsuka D, Nozawa K, Endo Y, Ozaki Y, et al. The frequency of low HER2 expression in breast cancer and a comparison of prognosis between patients with HER2-low and HER2-negative breast cancer by HR status. Breast Cancer. 2022;29(2):234-41. de Moura Leite L, Cesca MG, Tavares MC, Santana DM, Saldanha EF, Guimarães PT, et al. HER2-low status and response to neoadjuvant chemotherapy in HER2 negative early breast cancer. Breast Cancer Res Treat. 2021;190(1):155-63. Viale G, Basik M, Niikura N, Tokunaga E, Brucker S, Penault-Llorca F, et al. Retrospective study to estimate the prevalence and describe the clinicopathological characteristics, treatments received, and outcomes of HER2-low breast cancer. ESMO Open. 2023;8(4):101615. Park WK, Nam SJ, Kim SW, Lee JE, Yu J, Ryu JM, et al. The Impact of HER2-Low Expression on Oncologic Outcomes in Hormone Receptor-Positive Breast Cancer. Cancers (Basel). 2023;15(22). Cardoso F, Bartlett JMS, Slaets L, van Deurzen CHM, van Leeuwen-Stok E, Porter P, et al. Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Ann Oncol. 2018;29(2):405-17. Chavez-Macgregor M, Clarke CA, Lichtensztajn D, Hortobagyi GN, Giordano SH. Male breast cancer according to tumor subtype and race: a population-based study. Cancer. 2013;119(9):1611-7. Shaaban AM, Ball GR, Brannan RA, Cserni G, Di Benedetto A, Dent J, et al. A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences. Breast Cancer Res Treat. 2012;133(3):949-58. Smith L, Coleman LJ, Cummings M, Satheesha S, Shaw SO, Speirs V, et al. Expression of oestrogen receptor beta isoforms is regulated by transcriptional and post-transcriptional mechanisms. Biochem J. 2010;429(2):283-90. Al-Nakhle H, Burns PA, Cummings M, Hanby AM, Hughes TA, Satheesha S, et al. Estrogen receptor {beta}1 expression is regulated by miR-92 in breast cancer. Cancer Res. 2010;70(11):4778-84. Venema CM, Bense RD, Steenbruggen TG, Nienhuis HH, Qiu SQ, van Kruchten M, et al. Consideration of breast cancer subtype in targeting the androgen receptor. Pharmacol Ther. 2019;200:135-47. Elebro K, Borgquist S, Simonsson M, Markkula A, Jirström K, Ingvar C, et al. Combined Androgen and Estrogen Receptor Status in Breast Cancer: Treatment Prediction and Prognosis in a Population-Based Prospective Cohort. Clin Cancer Res. 2015;21(16):3640-50. Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, et al. Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer. Clin Cancer Res. 2013;19(19):5505-12. Lu Q, Xia W, Lee K, Zhang J, Yuan H, Yuan Z, et al. Bicalutamide plus Aromatase Inhibitor in Patients with Estrogen Receptor-Positive/Androgen Receptor-Positive Advanced Breast Cancer. Oncologist. 2020;25(1):21-e15. Palmieri C, Linden H, Birrell SN, Wheelwright S, Lim E, Schwartzberg LS, et al. Activity and safety of enobosarm, a novel, oral, selective androgen receptor modulator, in androgen receptor-positive, oestrogen receptor-positive, and HER2-negative advanced breast cancer (Study G200802): a randomised, open-label, multicentre, multinational, parallel design, phase 2 trial. Lancet Oncol. 2024;25(3):317-25. Di Lauro L, Barba M, Pizzuti L, Vici P, Sergi D, Di Benedetto A, et al. Androgen receptor and antiandrogen therapy in male breast cancer. Cancer Lett. 2015;368(1):20-5. Murphy CE, Carder PJ, Lansdown MR, Speirs V. Steroid hormone receptor expression in male breast cancer. Eur J Surg Oncol. 2006;32(1):44-7. Krop I, Abramson V, Colleoni M, Traina T, Holmes F, Garcia-Estevez L, et al. A Randomized Placebo Controlled Phase II Trial Evaluating Exemestane with or without Enzalutamide in Patients with Hormone Receptor-Positive Breast Cancer. Clin Cancer Res. 2020;26(23):6149-57. Xu H, Han Y, Wu Y, Wang Y, Li Q, Zhang P, et al. Clinicopathological Characteristics and Prognosis of HER2-Low Early-Stage Breast Cancer: A Single-Institution Experience. Front Oncol. 2022;12:906011. Li Y, Abudureheiyimu N, Mo H, Guan X, Lin S, Wang Z, et al. In Real Life, Low-Level HER2 Expression May Be Associated With Better Outcome in HER2-Negative Breast Cancer: A Study of the National Cancer Center, China. Front Oncol. 2021;11:774577. Tan R, Ong WS, Lee KH, Lim AH, Park S, Park YH, et al. HER2 expression, copy number variation and survival outcomes in HER2-low non-metastatic breast cancer: an international multicentre cohort study and TCGA-METABRIC analysis. BMC Med. 2022;20(1):105. Mutai R, Barkan T, Moore A, Sarfaty M, Shochat T, Yerushalmi R, et al. Prognostic impact of HER2-low expression in hormone receptor positive early breast cancer. Breast. 2021;60:62-9. Petrelli F, Rea C, Parati MC, Borgonovo K, Ghilardi M, Dottorini L, et al. Prognostic Value of HER2-low Status in ER+ Early Breast Cancer: A Systematic Review and Meta-Analysis. Anticancer Res. 2023;43(10):4303-13. Molinelli C, Jacobs F, Agostinetto E, Nader-Marta G, Ceppi M, Bruzzone M, et al. Prognostic value of HER2-low status in breast cancer: a systematic review and meta-analysis. ESMO Open. 2023;8(4):101592. Almstedt K, Heimes AS, Kappenberg F, Battista MJ, Lehr HA, Krajnak S, et al. Long-term prognostic significance of HER2-low and HER2-zero in node-negative breast cancer. Eur J Cancer. 2022;173:10-9. Hu XE, Yang P, Chen S, Wei G, Yuan L, Yang Z, et al. Clinical and biological heterogeneities in triple-negative breast cancer reveals a non-negligible role of HER2-low. Breast Cancer Res. 2023;25(1):34. Di Cosimo S, La Rocca E, Ljevar S, De Santis MC, Bini M, Cappelletti V, et al. Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real world. Front Mol Biosci. 2022;9:996434. Jacot W, Maran-Gonzalez A, Massol O, Sorbs C, Mollevi C, Guiu S, et al. Prognostic Value of HER2-Low Expression in Non-Metastatic Triple-Negative Breast Cancer and Correlation with Other Biomarkers. Cancers (Basel). 2021;13(23). Tarantino P, Jin Q, Tayob N, Jeselsohn RM, Schnitt SJ, Vincuilla J, et al. Prognostic and Biologic Significance of ERBB2-Low Expression in Early-Stage Breast Cancer. JAMA Oncol. 2022;8(8):1177-83. Johnston SR. New strategies in estrogen receptor-positive breast cancer. Clin Cancer Res. 2010;16(7):1979-87. Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2020;382(7):610-21. Cortés J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022;386(12):1143-54. Modi S, Park H, Murthy RK, Iwata H, Tamura K, Tsurutani J, et al. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study. J Clin Oncol. 2020;38(17):1887-96. Wang J, Liu Y, Zhang Q, Feng J, Fang J, Chen X, et al. RC48-ADC, a HER2-targeting antibody-drug conjugate, in patients with HER2-positive and HER2-low expressing advanced or metastatic breast cancer: a pooled analysis of two studies. Wolters Kluwer Health; 2021. Mosele F, Deluche E, Lusque A, Le Bescond L, Filleron T, Pradat Y, et al. Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial. Nat Med. 2023;29(8):2110-20. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6691251","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":465833395,"identity":"0524383d-a250-4dcb-a424-78d6238efb49","order_by":0,"name":"Qiang Sa","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Qiang","middleName":"","lastName":"Sa","suffix":""},{"id":465833400,"identity":"4402a62a-74ec-4494-9e85-14af243dc65c","order_by":1,"name":"Hangcheng Xu","email":"","orcid":"","institution":"National 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10:53:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6691251/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6691251/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84185800,"identity":"05baac15-1345-404b-ac0b-0dea3b966319","added_by":"auto","created_at":"2025-06-09 05:30:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":162632,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of the patient-screening process\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6691251/v1/3db06a1fa2b19732e4cdf9b2.png"},{"id":84185797,"identity":"e5b580e9-92cd-47be-9aa8-e695a921bbd1","added_by":"auto","created_at":"2025-06-09 05:30:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":249120,"visible":true,"origin":"","legend":"\u003cp\u003eComparative analysis of DFS (\u003cstrong\u003ea\u003c/strong\u003e) and OS (\u003cstrong\u003eb\u003c/strong\u003e) associated with HER2 status\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6691251/v1/38e50d315ed371e15a5d736a.png"},{"id":102310570,"identity":"a1a5bec5-cab7-4211-9e6a-1cdf60a59bf5","added_by":"auto","created_at":"2026-02-10 11:55:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1832025,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6691251/v1/e33a4a7d-25bd-4842-afa6-7195454ce68f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinicopathological Features and Prognostic Implications of HER2-Low in Early-Stage Male Breast Cancer: A Retrospective Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMale breast cancer is a rare disease accounting for less than 1% of all breast cancer cases(1), with its incidence gradually increasing(2). Owing to the rarity and lack of large-scale studies on male BC, current treatments are predominantly derived from those established for female BC. Research indicates that there are significant differences in the clinicopathological characteristics and survival outcomes between male and female patients with BC(1), underscoring the necessity for a deeper understanding of male BC.\u003c/p\u003e \u003cp\u003eBreast cancer subtypes are categorized on the basis of the status of hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2). Traditionally, breast cancers are classified as either HER2-positive or HER2-negative(3). For HER2-negative tumors, it was previously believed that these patients could not benefit from anti-HER2 treatments(4). However, with the advent of new drugs, a subset of HER2-negative cancers with low levels of HER2 expression, termed HER2-low, has shown a response to anti-HER2 antibody‒drug conjugates (ADCs), such as T-DXd(5). This advancement has changed the traditional binary classification of HER2 status.\u003c/p\u003e \u003cp\u003eCurrently, HER2-low breast cancer has been the focus of extensive research. This subtype represents a substantial portion, potentially accounting for up to half of all breast cancer cases(6). Compared to their HER2-zero counterparts, HER2-low tumors exhibit higher rates of HR positivity and different responses to treatment(7). A meta-analysis of 23 retrospective studies indicated that patients with HER2-low breast cancer have better DFS and OS in the early stage(6). However, research specifically on HER2-low male BC is limited. To date, only six studies have focused on or included this population, reporting that the proportion of HER2-low cases varies between 21% and 73%(8\u0026ndash;13). The specific characteristics and survival outcomes of HER2-low male BC remain underexplored. This comparative analysis aimed to determine whether HER2-low early-stage male BC represents a distinct clinical entity with unique prognostic implications.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Selection and Data Collection\u003c/h2\u003e \u003cp\u003eThis retrospective study reviewed patients who were diagnosed with breast cancer and hospitalized at our institution between January 2010 and September 2023. Among these patients, only male patients were included. Further exclusions were made on the basis of the following criteria: patients with advanced disease, HER2-positive or unknown HER2 status, intraductal carcinoma, unavailable medical records, and non-primary breast cancer. The enrolled patients were classified into two groups based on HER2 expression: HER2-zero and HER2-low.\u003c/p\u003e \u003cp\u003eWe extracted baseline clinicopathological features from the patients\u0026rsquo; electronic medical records. These features included age at diagnosis, family history of cancer, body mass index (BMI), comorbidities, tumor grade, TNM stage, estrogen receptor (ER) status, progesterone receptor (PR) status, AR status, Ki-67 index, and treatment modalities (including surgery, radiotherapy, and adjuvant chemotherapy). Survival status was determined through follow-up calls.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDefinition of Variables\u003c/h3\u003e\n\u003cp\u003eHER2 expression was assessed via immunohistochemistry (IHC) and categorized as follows: IHC 0, IHC 1+, IHC 2+, and IHC 3+. For patients with HER2 IHC 2\u0026thinsp;+\u0026thinsp;tumors, in situ hybridization (ISH) was conducted. Cases with an IHC score of 0 were defined as HER2-zero, whereas cases with an IHC score of 1\u0026thinsp;+\u0026thinsp;or an IHC score of 2+/ISH negative were defined as HER2-low. Tumor staging followed the American Joint Committee on Cancer (AJCC) staging system, seventh edition. ER and PR were considered positive if they exceeded 1%. HR status was deemed positive with ER and/or PR positivity and negative with both ER and PR negativity. The AR status was positive if it exceeded 10%. A high Ki-67 index was defined as greater than 20%. DFS was the interval from the completion of primary treatment to recurrence, distant metastasis, or death. OS was defined as the time from breast cancer diagnosis to death from any cause or the latest follow-up.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eClinicopathological features were summarized via descriptive statistics. Continuous variables were reported as means or medians, and categorical variables were reported as frequencies and percentages. We compared variable distributions between the HER2-zero and HER2-low groups via chi-square or Fisher\u0026rsquo;s exact tests for categorical variables and the Mann‒Whitney test for continuous variables. Survival probabilities were estimated via the Kaplan‒Meier method, with intergroup comparisons performed via log-rank tests. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors for DFS and OS. The results were expressed as hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Variables with P values\u0026thinsp;\u0026lt;\u0026thinsp;0.1 in the univariate analysis were included in the multivariate analysis. A P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to indicate statistical significance. Statistical analyses were conducted via SPSS version 23.0 (SPSS Inc., Chicago, IL, USA) and R Studio software, version 4.1.1.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003eBaseline Clinicopathological Characteristics\u003c/h2\u003e\n \u003cp\u003eAfter screening 38,632 breast cancer patients, we identified 133 male patients, accounting for 0.34% of all BC patients. Among these patients, 99 patients with non-HER2-positive tumors were included in the final analysis. These patients were further divided into two subgroups: 41 patients in the HER2-zero group and 58 patients in the HER2-low subgroup. The detailed screening process is illustrated in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The baseline characteristics of the two subgroups are presented in \u003cstrong\u003eTable\u0026nbsp;1\u003c/strong\u003e.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Comparative analysis of baseline characteristics between the HER2-zero and HER2-low subgroup\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Taba\" border=\"1\"\u003e\n \u003ccolgroup cols=\"6\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eHER2-zero (n\u0026thinsp;=\u0026thinsp;41)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eHER2-low (n\u0026thinsp;=\u0026thinsp;58)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo.\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePercentage (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo.\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePercentage (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at diagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (Range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e57 (34\u0026ndash;84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e59 (32\u0026ndash;81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.619\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e0.664\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35\u0026ndash;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eFamily history of cancer\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.830\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAverage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e25.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e25.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.563\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (Range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e25.46 (18.44\u0026ndash;34.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e24.51 (18.34\u0026ndash;37.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.471\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u0026thinsp;\u0026gt;\u0026thinsp;=\u0026thinsp;24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.836\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u0026thinsp;\u0026lt;\u0026thinsp;24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e0.879\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eT stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT0-T2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.473\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT3-T4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eN stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN0-N1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.311\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN2-N3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eTNM stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0-II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.200\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eER status (\u0026gt;\u0026thinsp;1%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e93.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.90\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePR status (\u0026gt;\u0026thinsp;1%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e89.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.732\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR status (\u0026gt;\u0026thinsp;1%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e94.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eAR status (\u0026gt;\u0026thinsp;10%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eKi-67 index (\u0026gt;\u0026thinsp;20%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubtype\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLuminal A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e0.896\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLuminal B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTriple-negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.90\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal mastectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e0.222\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eModified radical mastectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.90\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjuvant Radiotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003e0.165\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.90\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjuvant Chemotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.151\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eChemotherapy Regimens\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTaxane involved\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.499\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnthracycline involved\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.207\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlatinum-based\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.224\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.307\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHepatic disease\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.518\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCoronary artery disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.690\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCerebrovascular disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMalignant tumors of other types\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e*Abbreviations: ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e2; AR, androgen receptor; BMI, body mass index.\u003c/p\u003e\n \u003cp\u003e*Remarks: P values in bold indicate statistically significant results.\u003c/p\u003e\n \u003cp\u003e\u003csup\u003ea\u003c/sup\u003e Chemotherapy regimens may overlap with each other.\u003c/p\u003e\n \u003cp\u003e\u003csup\u003eb\u003c/sup\u003e Metastatic organs may overlap with each other.\u003c/p\u003e\n \u003cp\u003e\u003csup\u003ec\u003c/sup\u003e Hepatic disease includes fatty liver disease, viral hepatitis, and liver cirrhosis.\u003c/p\u003e\n \u003cp\u003eNo significant differences were observed between the two groups in terms of ER, PR, HR, or Ki-67 expression. However, the HER2-low group exhibited significantly higher AR expression (P\u0026thinsp;=\u0026thinsp;0.003). Other clinicopathological characteristics, including stage, BMI, treatment modality, and comorbidities, were similar between the two subgroups.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eSurvival Outcomes and Cox Regression Analysis\u003c/h2\u003e\n \u003cp\u003eThe median follow-up time for this study was 70 months. The analysis of DFS between the two subgroups did not reveal a statistically significant difference, although the median DFS in the HER2-low subgroup tended to be longer than that in the HER2-zero subgroup (not reached vs. 106 months, P\u0026thinsp;=\u0026thinsp;0.1). In terms of OS, the HER2-low subgroup had a significantly longer median OS than the HER2-zero subgroup (not reached vs. 121 months, P\u0026thinsp;=\u0026thinsp;0.01). The results of the survival analysis are illustrated in Figs. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ea and \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eb.\u003c/p\u003e\n \u003cp\u003eUnivariate and multivariate Cox regression analyses were performed, and the results are summarized in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Age, TNM stage, and endocrine therapy were included in further multivariate analysis for DFS, in which younger age (P\u0026thinsp;=\u0026thinsp;0.025) and TNM stage (P\u0026thinsp;=\u0026thinsp;0.047) were significant prognostic factors. The multivariate analysis of OS included age, TNM stage, HR status, and HER2 status, with HER2-low status (P\u0026thinsp;=\u0026thinsp;0.050) and younger age (P\u0026thinsp;=\u0026thinsp;0.026) being significant prognostic factors for better OS.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\" class=\"fr-table-selection-hover\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eUnivariate and multivariate analyses of variables correlated with DFS and OS in HER2-zero and HER2-low patients\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"9\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eUnivariate Analysis\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eMultivariate Analysis\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDFS\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eOS\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eDFS\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eOS\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHazard Ratio\u003c/p\u003e\n \u003cp\u003e(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHazard Ratio\u003c/p\u003e\n \u003cp\u003e(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHazard Ratio\u003c/p\u003e\n \u003cp\u003e(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep Value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHazard Ratio\u003c/p\u003e\n \u003cp\u003e(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, Years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;=55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003cp\u003e(0.14\u0026ndash;0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.018\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003cp\u003e(0.11\u0026ndash;0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.048\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003cp\u003e(0.14\u0026ndash;0.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.025\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;=60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003cp\u003e(0.23-1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.05\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003cp\u003e(0.14\u0026ndash;0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.018\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003cp\u003e(0.13\u0026ndash;0.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.026\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01\u003c/p\u003e\n \u003cp\u003e(0.48\u0026ndash;2.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.987\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.14\u003c/p\u003e\n \u003cp\u003e(0.48\u0026ndash;2.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.766\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eFamily history of cancer\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003cp\u003e(0.42\u0026ndash;2.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.860\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003cp\u003e(0.34\u0026ndash;2.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.808\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eFamily history of breast cancer\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003cp\u003e(0.23\u0026ndash;4.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.950\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.15\u003c/p\u003e\n \u003cp\u003e(0.15\u0026ndash;8.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.893\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eBody Mass Index (BMI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;=24.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003cp\u003e(0.47\u0026ndash;2.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.970\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003cp\u003e(0.30\u0026ndash;1.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.538\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eT stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT3-T4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT0-T2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003cp\u003e(0.16\u0026ndash;1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.090\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003cp\u003e(0.13\u0026ndash;1.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eN stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN2-N3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN0-N1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003cp\u003e(0.25\u0026ndash;1.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.189\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003cp\u003e(0.18\u0026ndash;1.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.158\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eTNM stage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eI-II\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003cp\u003e(0.24\u0026ndash;1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.096\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003cp\u003e(0.14\u0026ndash;0.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.035\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003cp\u003e(0.20\u0026ndash;0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.047\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003cp\u003e(0.20\u0026ndash;1.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.307\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eER status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003epositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.73\u003c/p\u003e\n \u003cp\u003e(0.52\u0026ndash;5.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.374\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.01\u003c/p\u003e\n \u003cp\u003e(0.46\u0026ndash;8.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.357\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003ePR status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003epositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.40\u003c/p\u003e\n \u003cp\u003e(0.82\u0026ndash;6.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.12\u003c/p\u003e\n \u003cp\u003e(1.31\u0026ndash;12.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003epositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003cp\u003e(0.47\u0026ndash;8.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.348\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.83\u003c/p\u003e\n \u003cp\u003e(0.85\u0026ndash;17.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.08\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.81\u003c/p\u003e\n \u003cp\u003e(0.37\u0026ndash;8.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.469\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eHER2 status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHER2-low\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHER2-0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.86\u003c/p\u003e\n \u003cp\u003e(0.87\u0026ndash;3.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.04\u003c/p\u003e\n \u003cp\u003e(1.20\u0026ndash;7.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.83\u003c/p\u003e\n \u003cp\u003e(1.00-7.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.050\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubtype\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLuminal A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.333\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLuminal B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.82\u003c/p\u003e\n \u003cp\u003e(0.77\u0026ndash;4.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.42\u003c/p\u003e\n \u003cp\u003e(0.50\u0026ndash;4.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.509\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTriple-negative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.41\u003c/p\u003e\n \u003cp\u003e(0.49\u0026ndash;11.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.277\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.27\u003c/p\u003e\n \u003cp\u003e(0.80-22.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eRadiotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003cp\u003e(0.26\u0026ndash;1.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.224\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003cp\u003e(0.19\u0026ndash;1.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.354\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjuvant chemotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.05\u003c/p\u003e\n \u003cp\u003e(0.50\u0026ndash;2.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.907\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003cp\u003e(0.41\u0026ndash;2.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003e\u003cstrong\u003eEndocrine therapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.17\u003c/p\u003e\n \u003cp\u003e(1.00-4.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.051\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.08\u003c/p\u003e\n \u003cp\u003e(1.29\u0026ndash;7.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.012\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.70\u003c/p\u003e\n \u003cp\u003e(0.75\u0026ndash;3.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn recent years, low HER2 expression has been a research focus in breast cancer. A variety of conclusions have been drawn from research on HER2-low female BC, but the issue has not been studied sufficiently in male patients. Our study investigated the factors related to the prognosis of male BC and focused on the characteristics of HER2-low male BC.\u003c/p\u003e \u003cp\u003eAge was an independent predictor for both DFS and OS in our male BC population. To our knowledge, younger age is a factor for poor prognosis in female BC(14). The association between younger age and poor prognosis in women is largely due to the pathogenic effect of estrogen before menopause. Natural menopause exempts later-diagnosed breast tumors from hormonal stimulation, thus decreasing the risk of recurrence and death. In contrast, other studies, including ours, suggest that older age is a risk factor for OS in male patients(15\u0026ndash;17). The different correlations between age and survival in male patients are likely due to the lack of age-dependent endocrine changes, as in female BC patients(18). The lower survival rates in older male BC patients, which resemble other tumor types, can also be attributed to the increase in mortality from other chronic diseases and decreased tolerance to anti-tumor therapy with aging(19).\u003c/p\u003e \u003cp\u003eApart from age, our finding of TNM stage indicating better survival corresponds with other retrospective studies. However, other reported characteristics, including the ER/PR status, histological grade, and triple-negative subtype, were not significant(16, 17, 20\u0026ndash;22). As reported, radical mastectomy, chemotherapy, radiotherapy, and endocrine therapy were associated with better OS, and radical mastectomy and endocrine therapy were associated with better DFS in male BC(23, 24), which was not observed in our study. Most studies did not distinguish the stage of disease, and in a study on early-stage male BC, PR positivity, chemotherapy, radiotherapy, and endocrine therapy were associated with better OS(23).\u003c/p\u003e \u003cp\u003eWe focused on the HER2-low population in male BC. According to the literature, the incidence of HER2-low BC varies with different HR statuses in females. The incidence of HER2-low BC is 45\u0026ndash;65%(25\u0026ndash;27) in females and 35\u0026ndash;72% (8, 10\u0026ndash;12) in males; in this study, the incidence of HER2-low BC was 48%. Among HR-positive female BC patients, HER2-low cases account for 60\u0026ndash;90%(4, 26, 28\u0026ndash;30), which is often higher than in HR-negative female BC patients(25, 26, 28). However, this conclusion does not seem to be as solid in males with BC. According to a retrospective study from the Korean Breast Cancer Society, the proportions of HER2-low patients were 33.6% and 23% in the HR-positive and HR-negative subgroups, respectively (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001)(13). In contrast, the incidence of HER2-low in HR-positive and HR-negative male BC in this study was 52.9% and 42.9% (p\u0026thinsp;=\u0026thinsp;0.30), respectively, without a significant disparity. Other studies are not considered due to inconclusive results.\u003c/p\u003e \u003cp\u003eThis indefiniteness is probably due to the higher incidence of HR positivity in male BC. The percentage of HR-positive males with BC was 93.7% in this study and 89\u0026ndash;99%(8, 10, 31, 32) in existing studies, which is significantly higher than the percentage of 60\u0026ndash;70% in females with BC. A study revealed that ERα clustered with PR and its isoforms in female BC, whereas ERα clustered with ERβ and AR in male BC(33), which could partially explain the increased HR expression in male BC. However, the role of ERβ has not been fully elucidated in both female and male BC patients and is possibly regulated by 3\u0026prime;-untranslated regions (UTRs)(34) and microRNAs(35). As the disparity in HR expression between the two subgroups in this study was not statistically significant, we did not distinguish different HR statuses in subsequent analyses.\u003c/p\u003e \u003cp\u003eThe correlation between AR expression and prognosis differs among BC subtypes. Retrospective studies have shown that a higher AR is associated with improved outcomes in ER+/HER2- female BC patients but with worse outcomes in HER2\u0026thinsp;+\u0026thinsp;patients(36, 37). Androgen receptor inhibitors of different mechanisms also act differently among subtypes. In female BC, second-generation androgen receptor antagonists have shown efficacy in triple-negative BC (38) but not in HR-positive BC(39). In contrast, evidence from a clinical trial demonstrated the efficacy of nonsteroidal selective androgen receptor modulators (SARMs) in HR-positive/HER2-negative female BC patients(40). Such varied roles of AR in different BC subtypes may be the result of potential complex crosstalk among the ER, AR, and HER2 pathways(25).\u003c/p\u003e \u003cp\u003eIn male BC patients, the incidence of AR positivity is 34\u0026ndash;95%(41, 42). Our study revealed greater AR expression in the HER2-low subgroup than in the HER2-zero subgroup, which has not yet been investigated in previous studies. A clinical trial featuring SARMs in HR+/HER2- metastatic male BC revealed a correlation between AR status and positive treatment outcomes(43). As HER2-low male BC patients have higher AR expression, SARMs may be a potential option for HR+/HER2-low male BC in the metastatic stage. However, as AR expression is not included in every IHC test, only 57% of the patients had a known AR status. More evidence is needed to confirm whether a definite correlation lies between the AR and HER2 pathways and whether AR expression holds a predictive value in the treatment of male BC in later stages.\u003c/p\u003e \u003cp\u003eIn addition to those mentioned above, other clinicopathological features were investigated. However, unlike disparities in HER2-low female BC, other features, such as the age at diagnosis and lymph node involvement, were found to be consistent in this study.\u003c/p\u003e \u003cp\u003eThe relationship between HER2-low status and survival in female BC has been controversial. Earlier studies on 9,872 and 1,150 early-stage female BC patients suggested that HER2-low patients have a worse prognosis than HER2-zero patients do. Two studies in our center on early-stage and metastatic female BC reported improved OS and 5-year DFS in HR-positive/HER2-low female BC (44, 45). Research in other institutions has reached similar conclusions regarding early-stage female BC(7, 13, 46), particularly in women with high genomic risk(47). The role of HER2-low status as a prognostic factor has also been controversial in previous studies on female BC. Some studies support the role of HER2-low status as a positive indicator of OS and/or DFS(48\u0026ndash;50); some studies have reached opposite conclusions(51, 52), whereas others have concluded that HER2-low status is irrelevant to survival(27, 53).\u003c/p\u003e \u003cp\u003eWith a median follow-up of 70 months, the HER2-low group in our study had a significantly longer OS compared to the HER2-zero group in the survival analysis. A tendency for longer DFS was also observed, although the difference was not significant. Accordingly, HER2-low status was also proven to be a dependent prognostic factor for better OS. However, recent studies on early-stage male BC have failed to prove a definite correlation between HER2-low status and survival. A recent study on 120 early-stage male BC patients from 1995\u0026ndash;2022 reported a tendency toward better survival in patients with HER2-zero BC, but the correlation was not statistically significant(9). Although the size of our sample is not as large, our population was screened from a relatively recent period and belongs to a different race. These factors may result in discrepant levels of pathological diagnosis and diverse genetic features, leading to different conclusions. Another study of 5235 early-stage BC patients reached an insignificant conclusion, but as male patients accounted for only 1.2% and 0.4% of the HER2-low and HER2-zero subgroup, respectively(54), and a subgroup analysis was not carried out in male patients, the conclusion of this study may not be generalizable to male BC patients. Only one study in male BC patients evaluated the prognostic role of HER2-low status via Cox regression analysis, and the results were not significant; however, the study population included only metastatic male BC patients(12).\u003c/p\u003e \u003cp\u003eWe attempted to analyse the possible reasons for our findings concerning HER2-low status and survival. Considering the higher HR expression in male BC, the cross-talk between HR and HER2 is likely to contribute to the better prognosis of HER2-low male BC(55). Another contributing factor is the dynamic nature of HER2 expression, including intratumoral heterogeneity, laboratory error, and the alteration of HER2 expression in primary and metastatic sites [34][35]. Future investigations on HER2-low patients should also consider these factors, and repeated biopsies should be performed if necessary. Given that this issue has rarely been investigated in male BC, our findings suggest that HER2-low male BC is unique in terms of prognosis in both male and female BC.\u003c/p\u003e \u003cp\u003eNewly emerged ADCs have demonstrated efficacy in HER2-low female BC(56\u0026ndash;59). In the DESTINY-Breast04 trial, the novel ADC T-DXd showed efficacy over standard chemotherapy in HER2-low advanced BC(5), expanding the scope of the application of novel ADC drugs in HER2-low breast cancer. However, the recently published D-B04 trial included only two men out of 557 randomized patients, and only one male patient participated in the DAISY trial(60). Given that male patients are rarely included in clinical trials and are insufficiently investigated in retrospective studies, our study provides supplements and updates to the research on HER2-low in male BC patients. To our knowledge, our study is the first to report a positive result in the prognostic role of HER2-low male BC in the Chinese population. Our findings on HER2-low male BC indicate that it is a unique entity in early-stage male BC, and the stratification of HER2 may be beneficial for refining treatment modalities for male BC. The distinctiveness of HER2-low BC also provides insight into novel treatment options for HER2-low male BC in the later metastatic stage, which is expected to be a promising topic for future research.\u003c/p\u003e \u003cp\u003eLimitations of this study include its retrospective nature, insufficient sample size, reliance on a single-center approach, incomplete patient information, and partial loss to follow-up.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study focused on the features of HER2-low early-stage male BC in a single institution. A significant difference in AR positivity was found, in favour of the HER2-low subgroup. Compared with the HER2-0 subgroup, the HER2-low subgroup had a better OS, and HER2-low status was determined to be an independent prognostic factor for OS but not for DFS.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eBC\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; Breast Cancer\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDFS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDisease-Free Survival\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOverall Survival\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAR\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAndrogen Receptor\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHormone Receptor\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eER\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEstrogen Receptor\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePR\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eProgesterone Receptor\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHER2\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHuman Epidermal Growth Factor Receptor 2\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eADCs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnti-HER2 Antibody‒Drug Conjugates \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBMI\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBody Mass Index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIHC\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eImmunohistochemistry\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eISH\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn Situ Hybridization\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAJCC\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmerican Joint Committee on Cancer\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHR\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHazard Ratio\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCI\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConfidence Interval\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUTRs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUntranslated Regions\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSARMs\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSelective Androgen Receptor Modulators\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the principles outlined in the Declaration of Helsinki. This study received approval from the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS), and all participants provided written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analysed during the current study are not publicly available due to patient privacy, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding \u003c/strong\u003e \u003c/p\u003e\n\u003cp\u003eThe study was supported by the CAMS Innovation Fund for Medical Sciences (CIFMS, 2021-I2M-1-014).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQiang Sa, Hangcheng Xu and Jiayu Wang designed the study. Qiang Sa and Hangcheng Xu did the literature search and wrote the manuscript. Yan Wang, Yiran Zhou and Yun Wu were responsible in data acquisition. Qiang Sa, Hangcheng Xu and Yan Wang analyzed and interpreted the study results. Jiayu Wang and Peng Yuan revised the manuscript. All authors had full access to all data and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eWang F, Shu X, Meszoely I, Pal T, Mayer IA, Yu Z, et al. Overall Mortality After Diagnosis of Breast Cancer in Men vs Women. JAMA Oncol. 2019;5(11):1589-96.\u003c/li\u003e\n \u003cli\u003eChen Z, Xu L, Shi W, Zeng F, Zhuo R, Hao X, et al. Trends of female and male breast cancer incidence at the global, regional, and national levels, 1990-2017. 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Clin Cancer Res. 2010;16(7):1979-87.\u003c/li\u003e\n \u003cli\u003eModi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2020;382(7):610-21.\u003c/li\u003e\n \u003cli\u003eCort\u0026eacute;s J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022;386(12):1143-54.\u003c/li\u003e\n \u003cli\u003eModi S, Park H, Murthy RK, Iwata H, Tamura K, Tsurutani J, et al. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study. J Clin Oncol. 2020;38(17):1887-96.\u003c/li\u003e\n \u003cli\u003eWang J, Liu Y, Zhang Q, Feng J, Fang J, Chen X, et al. RC48-ADC, a HER2-targeting antibody-drug conjugate, in patients with HER2-positive and HER2-low expressing advanced or metastatic breast cancer: a pooled analysis of two studies. Wolters Kluwer Health; 2021.\u003c/li\u003e\n \u003cli\u003eMosele F, Deluche E, Lusque A, Le Bescond L, Filleron T, Pradat Y, et al. Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial. Nat Med. 2023;29(8):2110-20.\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":"Male breast cancer, HER2-low, HER2-zero, Clinicopathologic features, Prognosis","lastPublishedDoi":"10.21203/rs.3.rs-6691251/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6691251/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e The clinicopathological and prognostic features of HER2-low female breast cancer (BC) patients have been widely studied. Current knowledge suggests that low HER2 expression could be identified as a special entity for treatment. However, research on HER2-low in early-stage male breast cancer remain limited.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis retrospective study screened male BC patients at a single institution between January 2010 and September 2023. Early-stage cases with non-HER2-positive tumors were included and categorized into HER2-low and HER2-zero groups. Clinicopathological features were collected and compared between the two groups. The primary endpoints were disease-free survival (DFS) and overall survival (OS). Statistical analysis was conducted viadescriptive statistics, the Kaplan‒Meier method with the log-rank test, and the Cox proportional hazards model to evaluate differences in DFS and OS between the groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eIn 99 early-stage non-HER2-positive male BC patients, 41 were classified as HER2-low, and 58 were classified as HER2-zero. In terms of clinicopathological features, the HER2-low subgroup exhibited higher androgen receptor (AR) expression (P=0.003). In terms of survival, no significant difference was observed in DFS (P=0.1), but the HER2-low subgroup had a significantly longer OS than the HER2-zero subgroup (P=0.01). Multivariate analysis revealed that age and TNM stage wereindependent prognostic factors for DFS, whereas age and HER2-low status were independent prognostic factors for OS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eIn early-stage male BC, the HER2-low population differed in clinicopathological features and prognostic role compared to HER2-zero counterparts. Compared with the HER2-zero subgroup, the HER2-low subgroup had a better OS, and HER2-low status was determined to be an independent prognostic factor for OS but not for DFS.\u003c/p\u003e","manuscriptTitle":"Clinicopathological Features and Prognostic Implications of HER2-Low in Early-Stage Male Breast Cancer: A Retrospective Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-09 05:30:10","doi":"10.21203/rs.3.rs-6691251/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":"d565e59c-2606-445e-a01a-e9dd5248973c","owner":[],"postedDate":"June 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-10T11:43:17+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-09 05:30:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6691251","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6691251","identity":"rs-6691251","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}