{"paper_id":"01c73235-981c-4c7f-8032-525b103590c7","body_text":"The Role of Adjuvant Radiotherapy in Low-Risk Elderly Male Breast Cancer: Is Omission Justified? | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Role of Adjuvant Radiotherapy in Low-Risk Elderly Male Breast Cancer: Is Omission Justified? Chang Xu, Cheng Zeng, Hanheng Meng, Fei Ma This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5285916/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The aim of our study is to evaluate the net survival benefit of adjuvant radiotherapy following breast-conserving surgery (BCS) in elderly male patients with early-stage, low-risk breast cancer (node-negative, hormone receptor-positive [HR+]) and to assess whether omitting radiotherapy might be a viable option based on observed survival outcomes. Methods We conducted a retrospective cohort study using data from SEER-17 registries (2000–2021), identifying 9,695 male breast cancer (MBC) patients. After applying inclusion criteria and PSM, a total of 360 patients were included. Early-stage, low-risk patients were categorized into radiotherapy (RT) and non-radiotherapy (NRT) groups. A 1:3 nearest neighbor propensity score matching (PSM; caliper = 0.05) was used to adjust for confounders. Estimate the net survival benefit of RT by using overall survival (OS), relative survival (RS), standardized mortality ratio (SMR), and transformed Cox regression, while controlling for background mortality. Results In early-stage, low-risk MBC patients underwent BCS, RT did not confer a significant survival benifit compared to those who omitted RT. After PSM adjustment, the 15-year OS, RS, and SMR for the RT group were 31.8%, 1.05, and 2.14, respectively, with no statistically significant differences observed when compared to the NRT group (34.1%, 1.03, and 2.25; p = 0.36, 0.35, and 0.81, respectively). Furthermore, the cumulative incidence of breast cancer-related death (BCRD) and non-BCRD did not differ significantly between the RT and NRT groups. The 15-year cumulative incidences of BCRD and non-BCRD were 7.0% and 61.2% in the RT group, and 12.4% and 53.5% in the NRT group (p = 0.06 and 0.75, respectively). Additionally, compared to the NRT group, the RT group demonstrated a lower risk for both OS and RS within the first 10 years following diagnosis, although this survival benefits gradually diminished over time. Conclusions In MBC patients over 65 with T 1 − 2 N 0 M 0 , hormone receptor-positive tumors, radiotherapy showed no significant improvement in overall, disease-specific, or net survival. Therefore, omitting radiotherapy may be justified for early-stage, low-risk patients, aligning treatment with individualized risk assessments. Male breast cancer Adjuvant radiotherapy Breast conserving surgery Systemic therapy SEER Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Although breast cancer is common among women, affecting about 1 in 8, male breast cancer (MBC) remains rare, accounting for only 1% of all cases, with a lifetime risk of approximately 1 in 1,000 for men [ 1 – 3 ]. While MBC shares some genetic and risk factors with female breast cancer (FBC) — such as personal, environmental, and age-related influences—it differs in key aspects, particularly in genetic mutations and biological characteristics [ 4 – 7 ]. MBC patients frequently present with advanced-stage disease and consequently have less favorable outcomes, perhaps due to inadequate awareness of the disease and psychosocial barriers that lead to diagnostic delays [ 8 – 12 ]. It is crucial, therefore, that treatments for MBC address not only the unique biological aspects of the disease but also the specific psychosocial dimensions associated with male patients [ 11 ]. Despite these needs, the differentiation between male and FBC is often neglected in clinical practice, with current therapeutic approaches for MBC largely extrapolated from guidelines established for FBC or aggregated from extensive literature reviews [ 4 ]. Furthermore, there is a deficiency of definitive data to guide the treatment of MBC, however, this deficiency cannot simply be attributed to the lower incidence of breast cancer in males. Adjuvant radiotherapy is a critical component of breast cancer treatment. The NCCN guidelines recommend treatment involving either mastectomy or breast-conserving surgery (BCS) plus adjuvant radiation for early-stage FBC patients[ 13 ]. In clinical practice for male patients, due to considerations of male breast anatomy, most men, including those diagnosed at an early stage, predominantly undergo mastectomy accompanied by axillary lymph node dissection or sentinel node biopsy, with adjuvant radiotherapy generally omitted [ 1 , 14 – 16 ]. For a minority of early-stage MBC patients who opt for BCS, the decision to administer postoperative radiotherapy is still contentious. Some radiation oncologists contend that the limited amount of breast tissue in males could result in insufficiently surgical margins, even for smaller tumors. As a result, they advocate for adjuvant radiotherapy to mitigate the risks associated with potentially inadequate margins [ 17 , 18 ]. In fact, treatment approaches for early-stage elderly FBC are increasingly focused on reducing the intensity of therapy, driven by advances in surgical techniques and systemic treatments such as hormone therapy [ 19 – 21 ]. Research suggests that omitting radiotherapy may be a viable option for women over 65 with low-risk, hormone receptor-positive early-stage breast cancer, as such omission has been shown not to adversely affect long-term overall survival rates and local control [ 22 , 23 ]. Given the higher incidence of hormone receptor positivity in MBC compared to their female counterparts, emerging studies indicate that early-stage MBC patients with negative surgical margins and hormone receptor-positive tumors may derive substantial benefit from maintenance therapy using tamoxifen following breast tumor resection [ 24 , 25 ]. Therefore, whether radiotherapy can be safely omitted in favor of hormone therapy for elderly, MBC patients with hormone receptor-positive tumors remains uncertain due to the limited data available. Some research on MBC comprises small-scale retrospective studies, which provide limited data on the survival benefits of omitting radiotherapy [ 15 , 26 , 27 ]. While studies utilizing large-scale, multicenter data from public databases have primarily concentrated on absolute survival, they often overlook in-depth examinations of net survival, disease-specific survival, and time-dependent survival following breast-conserving therapy [ 3 , 28 ]. Therefore, this study aims to analyze large-scale data from SEER databases to explore changes in absolute survival, disease-specific survival, net survival, and time-dependent survival among MBC patients undergoing post-lumpectomy radiotherapy. By examining these survival outcomes from various angles, we seek to ascertain survival outcomes for MBC patients who meet the current criteria for omitting radiotherapy. We hypothesize that omitting radiotherapy in early-stage, low-risk elderly MBC patients does not adversely affect long-term therapeutic outcomes. Methods Data source and patient selection The study population consisted of 9695 adult MBC as first primary cancer identified from the SEER-17 registries between 2000 and 2021. The male cohort exclusion criteria were: 1) Breast cancer was not the first primary cancer; 2) Without positive histology; 3) No breast conserving surgery or unknown surgery performed; 4)Not early-stage low-risk group (low-risk group defined as cases that meet all of the following criteria: age > 65 years, stage is T1-2N0M0, tumor size ≥ 3 cm, and hormone receptor-positive); 5) unknown cause of death; 6) unknown radiotherapeutic method; 7) Incomplete follow-up data. The flowchart of the inclusion and exclusion was presented in Fig. 1 (A). All the basic characteristics of patients were obtained from the SEER database. Endpoint and Definitions Early-stage, low-risk MBC in elderly patients is defined as hormone receptor-positive breast cancer in men aged over 65 years, with stage T1-2N0M0 disease and tumor size ≥ 3 cm. The primary endpoint of the study is overall survival (OS) and disease specific survival. Breast cancer related death (BCRD) was defined as patients dead from the disease. Non-BCRD was defined as patients dead from disease other than breast cancer. This classification was derived from the variables “SEER cause-specific death classification” and “SEER other cause of death classification” obtained from the SEER database. Patients with low-risk breast cancer were categorized into radiotherapy group (RT) and non-radiotherapy group (NRT). Age was categorized into two groups (> 75 or ≤ 75 years) Race was categorized into three groups: white, black, and other/unknown. Year of diagnosis was classified as 2000–2004, 2005–2010, 2011–2014 and 2015–2021. Statistical analysis To control for confounding and enhance the precision of treatment effect estimates, we employed a 1:3 nearest neighbor propensity score matching (PSM) approach with a caliper of 0.05. Key covariates included race, age, year of diagnosis, marital status, tumor T stage, clinical stage, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and tumor size. Propensity score matching was conducted under the constraint that control units that could not be adequately matched were discarded to maintain balance integrity. After matching, balance diagnostics were assessed using standardized mean differences (SMDs), with an SMD < 0.1 indicating acceptable covariate balance between treatment and control groups. Overall survival (OS) was defined as the time from diagnosis to death from any cause or the last follow-up date. The Kaplan-Meier method was used to estimate OS, and differences between groups were assessed using the log-rank test. The cumulative incidence of mortality by cause of death was analyzed using competing risks methodology, specifically employing Fine-Gray’s test. To assess the relative risk of BCRD and non-BCRD across different treatment groups, the sub-distribution hazard ratio (SHR) was calculated. The SHR quantifies the impact of covariates on the cumulative incidence function while accounting for competing risks, allowing for a direct comparison of the cumulative incidence of BCRD, considering the competing risk of non-breast-cancer-related deaths. The standardized mortality ratio (SMR) was determined by comparing the observed mortality in MBC patients to the expected mortality in a matched general population. Relative survival (RS) is defined as the ratio of observed survival in cancer patients to the expected survival in a comparable group from the general population. By applying a transformed Cox regression model for RS, excess mortality associated with the treatment group was assessed, accounting for population-specific risks and adjusting each patient's survival time to the corresponding expected mortality rate. Life tables and death rates used for calculating SMR and RS were sourced from U.S. population data. To assess the proportion and hazard ratio of BCRD and non-BCRD across the groups, splines were modeled with age as a continuous variable. The placement of spline knots was optimized using the C-index and Akaike Information Criterion (AIC) to ensure the best model fit. Categorical variables were compared using the chi-square test. All statistical analyses were conducted using R version 4.3.3 (R Foundation for Statistical Computing, Vienna, Austria), employing the tidycmprsk , survival , dplyr , mstate , cmprsk , survminer , riskRegression , cmprskcoxmsm , and splines packages. Data from the SEER database (SEER Research Data, 17 Registries, Nov 2023 Sub [2000–2021]) were retrieved using SEER*Stat software version 8.4.2. Results Baseline characteristics and treatment trend We initially identified 9,695 MBC patients from the SEER-17 database as the study population. Following the application of exclusion criteria, 765 early-stage, low-risk patients were included, with 95 patients in the radiotherapy (RT) group and 670 in the non-radiotherapy (NRT) group. To mitigate potential selection bias and address the imbalance in sample sizes between the treatment and control groups, we conducted a 1:3 PSM. After PSM, a total of 360 patients were retained, comprising 93 in the RT group and 267 in the NRT group. Baseline characteristics before PSM are presented in Table 1 , and the baseline characteristics after PSM are shown in Supplementary Table 1. The median age of the entire cohort before PSM was 75 years (range, 65–90), and 73 years (range, 65–90) after PSM. Stage I disease was observed in 68.4% and 70.8% of patients before and after PSM. After PSM, the distribution of characteristics between the treatment arms was well balanced (Fig. 1 (B)). Table 1 Baseline characteristics of early-stage low-risk male breast cancer patients stratified by primary treatment (2000–2021). Characteristic All patients No. (%) Treatment P value RT No. (%) NRT No. (%) Total 765 (100) 95 (100) 670 (100) - Age, years 0.027 Median age, year (range) 75 (65–90) 72 (65–90) 75 (65–90) 65–75 415 63 (66.3) 352 (52.5) > 75 350 32 (33.7) 318 (47.5) Gender - Male 765 (100) 95 (100) 670 (100) Clinical stage 0.804 I 523 (68.4) 66 (69.5) 457 (68.2) II 242 (31.6) 29 (30.5) 213 (31.8) pT stage 0.804 T1 523 (68.4) 66 (69.5) 457 (68.2) T2 242 (31.6) 29 (30.5) 213 (31.8) Tumor size 0.345 Median, mm (range) 18.0 (1.0–30.0) 17.0 (1.0–30.0) 18.0 (1.0–30.0) ER 0.004 Positive 3 (0.4) 2 (2.1) 1 (0.1) Negative 762 (99.6) 93 (97.9) 669 (99.9) PR 0.605 Positive 716 (93.6) 90 (94.7) 626 (93.4) Negative 38 (5.0) 5 (5.3) 33 (4.9) Unknown 11 (1.4) 0 (0) 11 (1.6) HER2 0.373 Positive 31 (4.1) 2 (2.1) 29 (4.3) Negative 477 (62.4) 59 (62.1) 418 (62.4) Unknown 257 (33.6) 34 (35.8) 223 (33.3) Year of diagnosis 0.580 2000–2005 111 (14.5) 15 (15.8) 96 (14.3) 2005–2010 172 (22.5) 23 (24.2) 149 (22.2) 2010–2015 238 (31.1) 28 (29.5) 210 (31.3) 2015–2021 244 (31.9) 29 (30.5) 215 (32.1) End point status 0.693 Alive 457 (59.7) 397 (59.3) 60 (63.2) Breast-cancer-related death (BCRD) 58 (7.6) 55 (8.2) 3 (3.2) Non-BCRD 250 (32.7) 32 (33.7) 218 (32.5) Race 0.469 White 666 (87.1) 81 (85.2) 585 (87.4) Black 50 (6.5) 11 (11.6) 39 (5.8) Other 46 (6.0) 3 (3.2) 43 (6.4) Unrecorded 3 (0.4) 0 (0) 3 (0.4) Marital status 0.871 Married 531 (69.4) 72 (75.8) 459 (68.5) Divorced/separated/widowed 134 (17.5) 14 (14.7) 120 (17.9) Single/unmarried/domestic partner 70 (9.2) 5 (5.3) 65 (9.7) Unrecorded 30 (3.9) 4 (4.2) 26 (3.9) The trend of treatment among early-stage MBC patients who underwent BCS is illustrated in Supplement Fig. 1 . The proportion of patients receiving RT remained consistently low, ranging from 10–25% throughout the study period, while the proportion of patients in the NRT group increased from 70% to nearly 90% by 2020. Notably, the RT group experienced minimal fluctuations, while the NRT group saw a steady rise, particularly after 2015. This trend suggests a shift in clinical practice towards more conservative treatment approaches, possibly influenced by the treatment strategies used in female cohorts, leading to the omission of adjuvant radiotherapy after BCS. Absolute overall survival analysis The median follow-up time for the entire cohort was 103 months, with 99 months for the RT group and 106 months for the NRT group. The overall survival of the groups was not continuously separated overtime both before and after PSM adjusted (Fig. 2 ). The unadjusted OS of 5-, 10-, 15-year were, respectively, 85.4%, 57.0% and 31.3% in RT group and 73.9%, 44.8% and 31.4% in NRT group (HR 0.78, 95%CI 0.55–1.10, p = 0.160; Fig. 2 (A)). The PSM-adjusted OS of 5-, 10-, 15-year were, respectively, 86.8%, 57.9% and 31.8% in RT group and 75.4%, 43.7% and 34.1% in NRT group (HR 0.83, 95%CI 0.57–1.23, p = 0.360; Fig. 2 (B)). To further minimize the impact of confounding factors, we performed a multivariable analysis based on Cox model. In this analysis, the use of RT had no significant effect on overall survival (HR 0.93, 95% CI 0.62–1.40; p = 0.73; Fig. 2 (C)). In disease specific analysis, RT showed limited impact on both breast cancer related death (BCRD) and non-BCRD. The cumulative incidence of breast cancer-related death (BCRD) at 5, 10 and 15 years was 0%, 3.9%, and 6.9%, respectively, in the RT group, compared to 6.7%, 10.7%, and 12.8% in the NRT group (SHR 0.95, 95% CI 0.74–1.23, p = 0.06; Fig. 3 (A)), before PSM adjustment. After PSM adjustment, the cumulative incidence remained similar, with rates of 0%, 3.9%, and 7.0% in the RT group, and 8.6%, 11.1%, and 12.4% in the NRT group (SHR 0.96, 95% CI 0.74–1.23, p = 0.06; Fig. 3 (B)). The unadjusted cumulative incidence of non-BCRD at 5-, 10-, 15-year were, respectively, 14.6%, 39.1%, and 61.9% in RT group and 19.4%, 44.5%, and 55.8% in NRT group (SHR 0.95, 95%CI 0.88–1.28, p = 0.84; Fig. 3 (C)), and 13.2%, 38.2%, and 61.2% in RT group and 16.0%, 45.2%, and 53.5% in NRT group after PSM adjusted (SHR 0.87, 95%CI 0.93–1.44, p = 0.75; Fig. 3 (D)). Net survival impact To minimize the impact of background mortality on overall survival, we assessed the net survival benefit of RT in comparison to the general population. In early-stage, low-risk MBC patients who did not receive adjuvant RT after BCS, no significant differences were observed in standardized mortality ratios (SMR) or relative survival (RS) compared to those who received RT. After PSM, the SMR of overall survival was 2.14 in the RT group and 2.25 in the NRT group (RR 0.95, 95% CI 0.65–1.40, p = 0.81; Fig. 4 (A)). Since the follow-up for the RT group did not extend to 20 years, the comparison focused on RS at 5, 10, and 15 years. During the observation period, RS remained stable in both the RT and NRT groups. After PSM, the 5-, 10-, and 15-year RS in the RT group were 1.044, 1.048, and 1.047, respectively, compared to 1.070, 1.051, and 1.031 in the NRT group (HR 0.83, 95% CI 0.57–1.23, p = 0.35; Fig. 4 (B)). To further explore the changes in dynamic radiotherapy-associated risk, we analyzed the relative risk (RR) at 5, 10, and 15 years after diagnosis. In the dynamic RR plot for BCRD (Supplement Fig. 2 (A)), the relative risk between the RT and NRT groups showed no significant increase in the RT group over time. At 5 years, the adjusted RR was 0.27 (95% CI, 0.06–1.18; p = 0.07), and at 10 years, the RR was 0.33 (95% CI, 0.10–1.10; p = 0.03). The risk remained relatively stable through 15 years, with an RR of 0.46 (95% CI, 0.39–1.26; p = 0.24). For non-BCRD (Supplement Fig. 2 (B)), the RT group demonstrated a stable relative risk in the early years, with an RR of 0.75 (95% CI, 0.37–1.52; p = 0.45) at 5 years and 0.70 (95% CI, 0.43–1.12; p = 0.35) at 10 years. However, by 15 years, there was an upward trend, with the adjusted RR reaching 1.20 (95% CI, 0.78–1.84; p = 0.68). Time dependent survival evaluation Based on the longitudinal assessment, the survival benefits of RT compared to non-RT group changed rapidly within the first 10 years after diagnosis (Fig. 5 ). The hazard ratios (HRs) for overall survival (OS) and relative survival (RS) changed over time, increasing from 0.658 and 0.572 at 1 year to 0.598 and 0.529 at 5 years, and further rising to 0.725 and 0.640 at 10 years, respectively. This finding underscores the necessity of a minimal 10-year follow-up to clearly identify the maximal survival differences and treatment benefits of radiotherapy compared to non-radiotherapy approaches, as demonstrated in the longitudinal data. Discussion With the rising incidence of breast cancer, particularly among the aging population [ 14 , 29 ], research is increasingly focused on treatment de-intensification for low-risk patients, such as those with low-grade, hormone receptor-positive disease [ 23 , 29 , 30 ], to minimize treatment burden, reduce side effects, and improve quality of life. Despite the relatively lower prevalence of MBC compared to its female counterpart, recent years have seen a notable rise in its incidence, emphasizing the need of developing tailored treatment strategies for MBC in medical research and clinical practice [ 31 , 32 ]. While these strategies have shown promise in FBC, it remains uncertain whether treatment de-intensification is equally applicable to MBC patients, given the unique biological and clinical characteristics of this population. Further research is required to evaluate the feasibility and outcomes of less intensive treatment approaches in MBC. Our study, utilizing data from SEER databases, evaluates the role of adjuvant radiotherapy in the management of hormone receptor-positive MBC patients aged over 65, diagnosed at an early stage (T 1 − 2 N 0 M 0 ), addressing the specific challenges associated with this population. Through a multi-faceted analysis involving absolute survival, net survival, and time-dependent survival, our findings suggest that radiotherapy does not confer additional survival benefits compared to its omission in early-stage low-risk MBC patients. In our study, RT use remained consistently low, while the NRT group showed a marked increase, particularly after 2015, reflecting the broader trend of radiotherapy de-escalation in breast cancer treatment. Studies like CALGB 9343 [ 30 ] and PRIME II [ 23 ] have demonstrated that omitting RT in low-risk, older female patients have no adverse effect on overall survival, while maintaining satisfactory local control. These findings, along with the 2017 NCCN guidelines, which introduced recommendations for omitting RT in low-risk female patients [ 29 ], likely contributed to the increasing trend of RT omission in MBC management. In our study involving low-risk elderly MBC patients, we found no significant differences between the RT and NRT groups in OS, RS, or disease-specific survival. The 15-year OS rate was 31.8% in the RT group compared to 34.1% in the NRT group. Even after PSM and further multivariable adjustment using Cox regression, these differences remained non-significant. These findings suggest that omitting radiotherapy may not negatively impact long-term survival in this patient cohort, aligning with the trend of treatment de-escalation observed in low-risk FBC populations. For example, both the CALGB 9343 and PRIME II studies demonstrated that in low-risk, elderly female patients, omitting radiotherapy does not negatively affect overall survival, while still maintaining satisfactory local control [ 23 , 30 ]. This provides strong support for treatment de-escalation in low-risk breast cancer patients. However, due to the biological and clinical differences between male and female breast cancer, the applicability of this conclusion in male patients requires careful evaluation. MBC tends to have a poorer prognosis and is often more aggressive, making it less straightforward to apply treatment strategies from FBC directly to male patient [ 5 , 33 , 34 ]. When discussing the impact of radiotherapy on BCRD, our findings did not show a significant reduction in risk. Similarly, results from the CALGB 9343 trial in female patients demonstrated that omitting radiotherapy had a relatively small effect on local recurrence rates in low-risk populations [ 30 ]. While radiotherapy may provide local control benefits in male patients, its effect on lowering breast cancer-specific mortality remains limited [ 30 ]. This is particularly relevant for older patients, where background mortality due to non-cancer-related factors like cardiovascular disease and other comorbidities becomes increasingly significant, reducing the potential survival benefit of radiotherapy [ 35 , 36 ]. As Giordano et al. highlighted, non-cancer-related deaths often become the predominant cause of mortality in elderly breast cancer patients, stressing the need for tailored treatment strategies in elderly MBC patients [ 6 ]. These findings reinforce the importance of personalized treatment approaches, particularly when weighing the benefits of radiotherapy against the increased risk of non-cancer mortality in this patient population. Further leveraging RS and SMR as endpoints to assess treatment-related adverse events and age-related background mortality, we found no significant differences between the RT and NRT groups. Notably, between the ages of 65 and 80, the SMR curves for both groups remained stable and closely aligned. However, after age 80, particularly beyond 85, the SMR for the NRT group rose significantly. This likely reflects the increasing influence of background mortality from non-cancer-related causes in the elderly, overshadowing the effect of radiotherapy on controlling breast cancer-specific mortality [ 37 ]. This suggests that in older populations, non-cancer-related factors play a more dominant role in survival outcomes, highlighting the need to carefully consider the utility of radiotherapy in these cases. The RR analysis in this study further supports this finding. For BCRD, no significant differences were observed between the RT and NRT groups. However, after 10 years, non-BCRD significantly increased in the NRT group, underscoring the importance of background mortality in elderly patients. Similar results have been reported in other studies on FBC, where the cardiovascular risks tend to increase over time, potentially offsetting the long-term benefits of radiotherapy [ 38 , 39 ]. After multivariable adjustment, we observed no significant differences in OS and RS between the RT and NRT groups throughout the 15-year follow-up period. Although radiotherapy appeared to confer a slight advantage in the first 10 years, this survival benefit diminished over time. This aligns with findings from some studies in female breast cancer, where the long-term impact of radiotherapy in low-risk patients has been shown to be limited, further supporting the rationale for omitting radiotherapy in certain cases [ 22 , 23 , 30 , 40 ]. Due to the limited data available on MBC, it is difficult to directly compare our results with other MBC studies, leaving us to rely on comparisons with female cohorts. Thus, caution is still needed when considering the omission of radiotherapy. At present, treatment de-intensification for elderly, low-risk patients have become a significant trend. This approach not only addresses the convenience of treatment and psychosocial factors for patients but also takes into account non-cancer-related mortality, which is particularly relevant in older populations. Current research is expanding beyond the omission of RT to consider the omission of endocrine therapy as well, given that MBC patients often show poor adherence to endocrine treatments [ 41 – 44 ]. However, most studies have excluded male cohorts, like the EUROPA trial [ 45 ], making it difficult to provide definitive information for MBC. Unfortunately, as the SEER database lacks information on endocrine therapy, we were unable to explore this aspect in our study. Although no statistically significant differences were observed between the RT and NRT groups in OS, net survival, or disease-specific survival in this study, treatment de-intensification in MBC, as emphasized in other research, should still be approached with caution. This study has some strengths. First, this study is a population-based analysis derived from a comprehensive public database, encompassing multicenter and multi-ethnic patient data, which provides robust insights into long-term survival outcomes across a diverse cohort. Second, our study employed a multifaceted analytical approach, evaluating OS, disease-specific survival, RS, SMR, and RR, offering a thorough assessment of the potential impact of radiotherapy from various perspectives. Third, PSM was used to minimize baseline differences between the RT and NRT groups, reducing potential confounding and allowing for a more accurate comparison of survival outcomes in low-risk MBC patients. This study has several limitations that should be acknowledged. First, the relatively small sample size, particularly in the RT group after PSM adjustment, may have reduced the statistical power to detect subtle differences between the groups. This is likely due to the limited use of BCS in MBC patients [ 4 , 46 , 47 ], as BCS is less common in men due to the small volume of breast tissue. In fact, only 4% − 19.8% of men with T1N0 tumors undergo BCS, which may have contributed to the low number of patients receiving adjuvant radiotherapy [ 46 – 48 ]. Additionally, the lack of established treatment guidelines specific to MBC may lead to variability in treatment decisions, potentially resulting in the underuse of radiotherapy. Previous studies, such as Bakalov et al., have shown that despite evidence suggesting radiotherapy can reduce mortality, a significant proportion of male BCS cases—about one-third—did not receive adjuvant RT [ 49 ]. This variability has increased the difficulty in obtaining relevant data for the RT group and further complicates the evaluation of RT's impact in this cohort. Second, the data derived from the SEER database may limit access to certain clinical details, such as radiotherapy fractionation, chemotherapy regimens and cycles, as well as endocrine therapy information. This lack of granularity restricts our ability to further analyze the relationship between treatment factors and survival outcomes. Third, as an observational retrospective study, it is challenging to control for residual confounding factors that may influence treatment outcomes, and thus, the conclusions drawn from this study require validation through larger randomized controlled trials. In conclusion, radiotherapy did not confer a significant survival benefit in MBC patients over 65 with T1-2N0M0, hormone receptor-positive tumors. Further randomized controlled trials are warranted to confirm these findings, with particular attention to the role of endocrine therapy. Despite the rarity of MBC, prospective studies remain essential to fully evaluate the long-term risks and benefits of radiotherapy in this patient population. Declarations Author Contribution Chang Xu: Conceptualization, Methodology, Formal analysis, Writing - Original DraftCheng Zeng: Methodology, Formal analysis,Writing - Original DraftHanheng Meng: Project administration, Writing - Review & EditingFei Ma: Supervision, Validation, Writing - Review & Editing References Lin AP, Huang TW, Tam KW (2021) Treatment of male breast cancer: meta-analysis of real-world evidence. Br J Surg 108(9):1034–1042 Fentiman IS, Fourquet A, Hortobagyi GN (2006) Male breast cancer. Lancet 367(9510):595–604 Vo K, Ladbury C, Yoon S, Bazan J, Glaser S, Amini A (2024) Omission of adjuvant radiotherapy in low-risk elderly males with breast cancer. Breast Cancer 31(3):485–495 Ruddy KJ, Winer EP (2013) Male breast cancer: risk factors, biology, diagnosis, treatment, and survivorship. 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J Breast Imaging 5(3):339–345 Altiner S, Altiner ÖT, Büyükkasap Ç, Uğraş Dikmen A, Pekcici MR, Erel S (2023) Analysis of Knowledge About Male Breast Cancer Among Patients at Tertiary Medical Center. Am J Mens Health 17(2):15579883231165626 Gradishar WJ, Moran MS, Abraham J, Abramson V, Aft R, Agnese D, Allison KH, Anderson B, Bailey J, Burstein HJ et al (2024) Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 22(5):331–357 Chidambaram A, Prabhakaran R, Sivasamy S, Kanagasabai T, Thekkumalai M, Singh A, Tyagi MS, Dhandayuthapani S (2024) Male Breast Cancer: Current Scenario and Future Perspectives. Technol Cancer Res Treat 23:15330338241261836 Rogowski P, Schönecker S, Pazos M, Reitz D, Braun M, Pölcher M, Hanusch C, Wuerstlein R, Harbeck N, Mahner S et al (2019) Pattern of care of adjuvant radiotherapy in male breast cancer patients in clinical practice: an observational study. Strahlenther Onkol 195(4):289–296 Yadav S, Karam D, Bin Riaz I, Xie H, Durani U, Duma N, Giridhar KV, Hieken TJ, Boughey JC, Mutter RW et al (2020) Male breast cancer in the United States: Treatment patterns and prognostic factors in the 21st century. Cancer 126(1):26–36 Yu E, Suzuki H, Younus J, Elfiki T, Stitt L, Yau G, Vujovic O, Perera F, Lock M, Tai P (2012) The impact of post-mastectomy radiation therapy on male breast cancer patients–a case series. Int J Radiat Oncol Biol Phys 82(2):696–700 Stranzl H, Mayer R, Quehenberger F, Prettenhofer U, Willfurth P, Stöger H, Hackl A (1999) Adjuvant radiotherapy in male breast cancer. Radiother Oncol 53(1):29–35 Mann GB, Skandarajah AR, Zdenkowski N, Hughes J, Park A, Petrie D, Saxby K, Grimmond SM, Murugasu A, Spillane AJ et al (2024) Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): primary results of a prospective two-arm study. Lancet 403(10423):261–270 Kouhen F (2023) Omitting radiotherapy in elderly breast cancer patients: Valid strategy or illusory hope? Breast 72:103598 Haque W, Verma V, Butler EB, Teh BS (2018) Omission of radiotherapy in elderly women with early stage metaplastic breast cancer. Breast 38:154–159 Kunkler IH, Williams LJ, Jack WJL, Cameron DA, Dixon JM (2023) Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer. N Engl J Med 388(7):585–594 Kunkler IH, Williams LJ, Jack WJL, Cameron DA, Dixon JM (2015) Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol 16(3):266–273 Slamon D, Lipatov O, Nowecki Z, McAndrew N, Kukielka-Budny B, Stroyakovskiy D, Yardley DA, Huang C-S, Fasching PA, Crown J et al (2024) Ribociclib plus Endocrine Therapy in Early Breast Cancer. N Engl J Med 390(12):1080–1091 Reinisch M, Seiler S, Hauzenberger T, Kamischke A, Schmatloch S, Strittmatter H-J, Zahm D-M, Thode C, Furlanetto J, Strik D et al (2021) Efficacy of Endocrine Therapy for the Treatment of Breast Cancer in Men: Results from the MALE Phase 2 Randomized Clinical Trial. JAMA Oncol 7(4):565–572 Arslan UY, Oksüzoğlu B, Ozdemir N, Aksoy S, Alkış N, Gök A, Kaplan MA, Gümüş M, Berk V, Uncu D et al (2012) Outcome of non-metastatic male breast cancer: 118 patients. Med Oncol 29(2):554–560 Fouhi ME, Mesfioui A, Benider A (2020) Male breast cancer: a report of 25 cases. Pan Afr Med J 37:343 Madden NA, Macdonald OK, Call JA, Schomas DA, Lee CM, Patel S (2016) Radiotherapy and Male Breast Cancer: A Population-based Registry Analysis. Am J Clin Oncol 39(5):458–462 Biganzoli L, Battisti NML, Wildiers H, McCartney A, Colloca G, Kunkler IH, Cardoso M-J, Cheung K-L, de Glas NA, Trimboli RM et al (2021) Updated recommendations regarding the management of older patients with breast cancer: a joint paper from the European Society of Breast Cancer Specialists (EUSOMA) and the International Society of Geriatric Oncology (SIOG). Lancet Oncol 22(7):e327–e340 Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, Muss HB, Smith BL, Hudis CA, Winer EP et al (2013) Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol 31(19):2382–2387 Reddington R, Galer M, Hagedorn A, Liu P, Barrack S, Husain E, Sharma R, Speirs V, Masannat Y (2020) Incidence of male breast cancer in Scotland over a twenty-five-year period (1992–2017). Eur J Surg Oncol 46(8):1546–1550 Mukherjee AG, Gopalakrishnan AV, Jayaraj R, Renu K, Dey A, Vellingiri B, Malik T (2023) The incidence of male breast cancer: from fiction to reality - correspondence. Int J Surg 109(9):2855–2858 Gwark S, Kim J, Chung IY, Kim HJ, Ko BS, Lee JW, Son BH, Ahn SH, Lee SB (2024) Survival pattern in male breast cancer: distinct from female breast cancer. Front Oncol 14:1392592 Gnerlich JL, Deshpande AD, Jeffe DB, Seelam S, Kimbuende E, Margenthaler JA (2011) Poorer survival outcomes for male breast cancer compared with female breast cancer may be attributable to in-stage migration. Ann Surg Oncol 18(7):1837–1844 Jørgensen TL, Hallas J, Friis S, Herrstedt J (2012) Comorbidity in elderly cancer patients in relation to overall and cancer-specific mortality. Br J Cancer 106(7):1353–1360 de Glas NA, Kiderlen M, Vandenbroucke JP, de Craen AJM, Portielje JEA, van de Velde CJH, Liefers G-J, Bastiaannet E, Le Cessie S (2016) Performing Survival Analyses in the Presence of Competing Risks: A Clinical Example in Older Breast Cancer Patients. J Natl Cancer Inst 108(5) Yang P, Zheng Y, Chen J, Ma H, Yu K, Chen Y, Yang Y, Wu B (2021) Immediate risk of non-cancer deaths after a cancer diagnosis. BMC Cancer 21(1):963 Hooning MJ, Botma A, Aleman BMP, Baaijens MHA, Bartelink H, Klijn JGM, Taylor CW, van Leeuwen FE (2007) Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst 99(5):365–375 Bouchardy C, Rapiti E, Usel M, Majno SB, Vlastos G, Benhamou S, Miralbell R, Neyroud-Caspar I, Verkooijen HM, Vinh-Hung V (2010) Excess of cardiovascular mortality among node-negative breast cancer patients irradiated for inner-quadrant tumors. Ann Oncol 21(3):459–465 Whelan TJ, Smith S, Parpia S, Fyles AW, Bane A, Liu F-F, Rakovitch E, Chang L, Stevens C, Bowen J et al (2023) Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer. N Engl J Med 389(7):612–619 Demissie S, Silliman RA, Lash TL (2001) Adjuvant tamoxifen: predictors of use, side effects, and discontinuation in older women. J Clin Oncol 19(2):322–328 Pemmaraju N, Munsell MF, Hortobagyi GN, Giordano SH (2012) Retrospective review of male breast cancer patients: analysis of tamoxifen-related side-effects. Ann Oncol 23(6):1471–1474 Venigalla S, Carmona R, Guttmann DM, Jain V, Freedman GM, Clark AS, Shabason JE (2018) Use and Effectiveness of Adjuvant Endocrine Therapy for Hormone Receptor-Positive Breast Cancer in Men. JAMA Oncol 4(10):e181114 Anelli TF, Anelli A, Tran KN, Lebwohl DE, Borgen PI (1994) Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients. Cancer 74(1):74–77 Meattini I, Poortmans PMP, Marrazzo L, Desideri I, Brain E, Hamaker M, Lambertini M, Miccinesi G, Russell N, Saieva C et al (2021) Exclusive endocrine therapy or partial breast irradiation for women aged ≥ 70 years with luminal A-like early stage breast cancer (NCT04134598 - EUROPA): Proof of concept of a randomized controlled trial comparing health related quality of life by patient reported outcome measures. J Geriatr Oncol 12(2):182–189 Chichura A, Attai DJ, Kuchta K, Nicholson K, Kopkash K, Pesce C, Yao K (2022) Male Breast Cancer Patient and Surgeon Experience: The Male WhySurg Study. Ann Surg Oncol 29(10):6115–6131 Elmi M, Sequeira S, Azin A, Elnahas A, McCready DR, Cil TD (2018) Evolving surgical treatment decisions for male breast cancer: an analysis of the National Surgical Quality Improvement Program (NSQIP) database. Breast Cancer Res Treat 171(2):427–434 Leone JP, Leone J, Zwenger AO, Iturbe J, Leone BA, Vallejo CT (2017) Locoregional treatment and overall survival of men with T1a,b,cN0M0 breast cancer: A population-based study. Eur J Cancer 71 Bakalov V, Jayakrishnan TT, Abel S, Hilton C, Rusia B, Wegner RE (2021) The use of adjuvant radiation therapy in male breast cancer and its impact on outcomes. Cancer Treat Res Commun 27:100359 Additional Declarations No competing interests reported. Supplementary Files FigureS1.tif FigureS2.tif Supplement.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies 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-5285916\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":367656682,\"identity\":\"2812ed4b-37f3-41ee-80b1-ecf6d028b40a\",\"order_by\":0,\"name\":\"Chang Xu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"National Cancer Center, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Chang\",\"middleName\":\"\",\"lastName\":\"Xu\",\"suffix\":\"\"},{\"id\":367656685,\"identity\":\"9c9045ce-abc2-46c4-981e-59f2c71e9990\",\"order_by\":1,\"name\":\"Cheng Zeng\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"National Cancer Center, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Cheng\",\"middleName\":\"\",\"lastName\":\"Zeng\",\"suffix\":\"\"},{\"id\":367656687,\"identity\":\"eb975e34-7b8c-4d8b-8e14-933d600ef2cf\",\"order_by\":2,\"name\":\"Hanheng Meng\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"The Second People’s Hospital of Datong Cancer Hospital, Shanxi Datong University Affiliated Cancer Hospital\",\"correspondingAuthor\":false,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hanheng\",\"middleName\":\"\",\"lastName\":\"Meng\",\"suffix\":\"\"},{\"id\":367656688,\"identity\":\"7ce1142e-1fa1-44e1-919e-07173567faf8\",\"order_by\":3,\"name\":\"Fei Ma\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAs0lEQVRIiWNgGAWjYNACGwYefmbmww9I0JLGwCPZzpZmQJIWBoPzPAoSRCk2Zz/8dMOPBBsZ48M8DAYMNTbRBLVY9qSZ3exJSOMxO8x74AHDsbTcBkJaDG7wsN3g/XEYqIUvwYCx4TBxWm7+SfjPY9zMYyBBtJbbPAkHeAyYidZyJs3stkxCMo/EYWAgJxDll+OHn918k2Bnz99/+PCDDzU2hLWgggTSlI+CUTAKRsEowAUAEK07ywRiToUAAAAASUVORK5CYII=\",\"orcid\":\"\",\"institution\":\"National Cancer Center, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)\",\"correspondingAuthor\":true,\"submittingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Fei\",\"middleName\":\"\",\"lastName\":\"Ma\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2024-10-18 02:53:13\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-5285916/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-5285916/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":67294650,\"identity\":\"7c36c3c8-48ee-4ea5-a095-07f7ad9dc3c6\",\"added_by\":\"auto\",\"created_at\":\"2024-10-23 10:46:45\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":1480158,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e(A) Patient selection flowchart, and (B) Clinical characteristics with absolute standardized mean differences between treatment arms before propensity score matching (PSM).\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"OnlineFigure1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5285916/v1/3ad2bc77d1cbbba8242b274c.png\"},{\"id\":67294655,\"identity\":\"653e5f59-6a65-4569-acf3-c153a39a844b\",\"added_by\":\"auto\",\"created_at\":\"2024-10-23 10:46:45\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":891202,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e(A) Kaplan-Meier curves for overall survival (OS) before and after propensity score matching (PSM) and multivariable adjustment based on Cox regression. (A) OS before PSM; (B) OS after PSM and (C) OS after balancing with PSM and adjusting for age, race, diagnosis year, hormone receptor status and marital status based on the Cox multivariable regression.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"OnlineFigure2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5285916/v1/8923432d7ecab85cea1cd0b4.png\"},{\"id\":67295434,\"identity\":\"f2f80e60-9bf8-4160-a2e7-d0fb773ee17d\",\"added_by\":\"auto\",\"created_at\":\"2024-10-23 10:54:45\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":565259,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eCumulative incidence curves for breast cancer-related death (BCRD) and non-breast cancer-related death (non-BCRD) before and after propensity score matching. (A) Cumulative incidence of BCRD before PSM. (B) Cumulative incidence of BCRD after PSM. (C) Cumulative incidence of non-BCRD before PSM. (D) Cumulative incidence of non-BCRD after PSM.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"OnlineFigure3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5285916/v1/29ff8512268ab10f02aced04.png\"},{\"id\":67295431,\"identity\":\"62d07c96-22ea-4d91-9357-364c17d10cf4\",\"added_by\":\"auto\",\"created_at\":\"2024-10-23 10:54:45\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":451566,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eComparison of Standardized Mortality Ratios (SMR) and Relative Survival (RS) between radiotherapy (RT) and non-radiotherapy (NRT) groups. (A) SMR curves for the RT and NRT groups plotted against age at diagnosis. (B) RS curves for the RT and NRT groups plotted over time after diagnosis.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"OnlineFigure4.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5285916/v1/5cee17340f87ac7111f23cba.png\"},{\"id\":67294657,\"identity\":\"dfbfbc97-bc32-4292-97bc-6e07cb950f9a\",\"added_by\":\"auto\",\"created_at\":\"2024-10-23 10:46:45\",\"extension\":\"png\",\"order_by\":5,\"title\":\"Figure 5\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":307819,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eAdjusted Hazard Ratios (HR) for Overall Survival (OS) and Relative Survival (RS) in the RT and NRT groups over time. (A) Adjusted HR for OS between the RT and NRT groups. (B) Adjusted HR for RS between the RT and NRT groups.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"OnlineFigure5.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5285916/v1/8cda4506f6a3ea360e4147ef.png\"},{\"id\":68564058,\"identity\":\"75e49c2e-a924-477a-9eeb-f80b79debbae\",\"added_by\":\"auto\",\"created_at\":\"2024-11-08 14:47:11\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1459771,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5285916/v1/0b18705c-375d-4b46-8e67-438919ad0d16.pdf\"},{\"id\":67295671,\"identity\":\"18d273dd-daf9-4080-bb98-00eb49a47abd\",\"added_by\":\"auto\",\"created_at\":\"2024-10-23 11:02:45\",\"extension\":\"tif\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":465864,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"FigureS1.tif\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5285916/v1/a90e1714e80fa166bd860042.tif\"},{\"id\":67295433,\"identity\":\"11459105-139e-4f30-a326-27febfc170e7\",\"added_by\":\"auto\",\"created_at\":\"2024-10-23 10:54:45\",\"extension\":\"tif\",\"order_by\":2,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":504691,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"FigureS2.tif\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5285916/v1/15f8e3f2fda8822024499e52.tif\"},{\"id\":67294651,\"identity\":\"aacdffe3-3c90-4e89-a4b1-e7f7e0eb6680\",\"added_by\":\"auto\",\"created_at\":\"2024-10-23 10:46:45\",\"extension\":\"docx\",\"order_by\":3,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":26678,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Supplement.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5285916/v1/10a9be05c5e129b08f641565.docx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"The Role of Adjuvant Radiotherapy in Low-Risk Elderly Male Breast Cancer: Is Omission Justified?\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eAlthough breast cancer is common among women, affecting about 1 in 8, male breast cancer (MBC) remains rare, accounting for only 1% of all cases, with a lifetime risk of approximately 1 in 1,000 for men [\\u003cspan additionalcitationids=\\\"CR2\\\" citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. While MBC shares some genetic and risk factors with female breast cancer (FBC) \\u0026mdash; such as personal, environmental, and age-related influences\\u0026mdash;it differs in key aspects, particularly in genetic mutations and biological characteristics [\\u003cspan additionalcitationids=\\\"CR5 CR6\\\" citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. MBC patients frequently present with advanced-stage disease and consequently have less favorable outcomes, perhaps due to inadequate awareness of the disease and psychosocial barriers that lead to diagnostic delays [\\u003cspan additionalcitationids=\\\"CR9 CR10 CR11\\\" citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. It is crucial, therefore, that treatments for MBC address not only the unique biological aspects of the disease but also the specific psychosocial dimensions associated with male patients [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]. Despite these needs, the differentiation between male and FBC is often neglected in clinical practice, with current therapeutic approaches for MBC largely extrapolated from guidelines established for FBC or aggregated from extensive literature reviews [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. Furthermore, there is a deficiency of definitive data to guide the treatment of MBC, however, this deficiency cannot simply be attributed to the lower incidence of breast cancer in males.\\u003c/p\\u003e \\u003cp\\u003eAdjuvant radiotherapy is a critical component of breast cancer treatment. The NCCN guidelines recommend treatment involving either mastectomy or breast-conserving surgery (BCS) plus adjuvant radiation for early-stage FBC patients[\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e]. In clinical practice for male patients, due to considerations of male breast anatomy, most men, including those diagnosed at an early stage, predominantly undergo mastectomy accompanied by axillary lymph node dissection or sentinel node biopsy, with adjuvant radiotherapy generally omitted [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan additionalcitationids=\\\"CR15\\\" citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]. For a minority of early-stage MBC patients who opt for BCS, the decision to administer postoperative radiotherapy is still contentious. Some radiation oncologists contend that the limited amount of breast tissue in males could result in insufficiently surgical margins, even for smaller tumors. As a result, they advocate for adjuvant radiotherapy to mitigate the risks associated with potentially inadequate margins [\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eIn fact, treatment approaches for early-stage elderly FBC are increasingly focused on reducing the intensity of therapy, driven by advances in surgical techniques and systemic treatments such as hormone therapy [\\u003cspan additionalcitationids=\\\"CR20\\\" citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]. Research suggests that omitting radiotherapy may be a viable option for women over 65 with low-risk, hormone receptor-positive early-stage breast cancer, as such omission has been shown not to adversely affect long-term overall survival rates and local control [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]. Given the higher incidence of hormone receptor positivity in MBC compared to their female counterparts, emerging studies indicate that early-stage MBC patients with negative surgical margins and hormone receptor-positive tumors may derive substantial benefit from maintenance therapy using tamoxifen following breast tumor resection [\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e]. Therefore, whether radiotherapy can be safely omitted in favor of hormone therapy for elderly, MBC patients with hormone receptor-positive tumors remains uncertain due to the limited data available.\\u003c/p\\u003e \\u003cp\\u003eSome research on MBC comprises small-scale retrospective studies, which provide limited data on the survival benefits of omitting radiotherapy [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e]. While studies utilizing large-scale, multicenter data from public databases have primarily concentrated on absolute survival, they often overlook in-depth examinations of net survival, disease-specific survival, and time-dependent survival following breast-conserving therapy [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e]. Therefore, this study aims to analyze large-scale data from SEER databases to explore changes in absolute survival, disease-specific survival, net survival, and time-dependent survival among MBC patients undergoing post-lumpectomy radiotherapy. By examining these survival outcomes from various angles, we seek to ascertain survival outcomes for MBC patients who meet the current criteria for omitting radiotherapy. We hypothesize that omitting radiotherapy in early-stage, low-risk elderly MBC patients does not adversely affect long-term therapeutic outcomes.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eData source and patient selection\\u003c/h2\\u003e \\u003cp\\u003eThe study population consisted of 9695 adult MBC as first primary cancer identified from the SEER-17 registries between 2000 and 2021. The male cohort exclusion criteria were: 1) Breast cancer was not the first primary cancer; 2) Without positive histology; 3) No breast conserving surgery or unknown surgery performed; 4)Not early-stage low-risk group (low-risk group defined as cases that meet all of the following criteria: age\\u0026thinsp;\\u0026gt;\\u0026thinsp;65 years, stage is T1-2N0M0, tumor size\\u0026thinsp;\\u0026ge;\\u0026thinsp;3 cm, and hormone receptor-positive); 5) unknown cause of death; 6) unknown radiotherapeutic method; 7) Incomplete follow-up data. The flowchart of the inclusion and exclusion was presented in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e(A). All the basic characteristics of patients were obtained from the SEER database.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\\n\\u003ch3\\u003eEndpoint and Definitions\\u003c/h3\\u003e\\n\\u003cp\\u003eEarly-stage, low-risk MBC in elderly patients is defined as hormone receptor-positive breast cancer in men aged over 65 years, with stage T1-2N0M0 disease and tumor size\\u0026thinsp;\\u0026ge;\\u0026thinsp;3 cm. The primary endpoint of the study is overall survival (OS) and disease specific survival. Breast cancer related death (BCRD) was defined as patients dead from the disease. Non-BCRD was defined as patients dead from disease other than breast cancer. This classification was derived from the variables \\u0026ldquo;SEER cause-specific death classification\\u0026rdquo; and \\u0026ldquo;SEER other cause of death classification\\u0026rdquo; obtained from the SEER database. Patients with low-risk breast cancer were categorized into radiotherapy group (RT) and non-radiotherapy group (NRT). Age was categorized into two groups (\\u0026gt;\\u0026thinsp;75 or \\u0026le;\\u0026thinsp;75 years) Race was categorized into three groups: white, black, and other/unknown. Year of diagnosis was classified as 2000\\u0026ndash;2004, 2005\\u0026ndash;2010, 2011\\u0026ndash;2014 and 2015\\u0026ndash;2021.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical analysis\\u003c/h2\\u003e \\u003cp\\u003eTo control for confounding and enhance the precision of treatment effect estimates, we employed a 1:3 nearest neighbor propensity score matching (PSM) approach with a caliper of 0.05. Key covariates included race, age, year of diagnosis, marital status, tumor T stage, clinical stage, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and tumor size. Propensity score matching was conducted under the constraint that control units that could not be adequately matched were discarded to maintain balance integrity. After matching, balance diagnostics were assessed using standardized mean differences (SMDs), with an SMD\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.1 indicating acceptable covariate balance between treatment and control groups. Overall survival (OS) was defined as the time from diagnosis to death from any cause or the last follow-up date. The Kaplan-Meier method was used to estimate OS, and differences between groups were assessed using the log-rank test. The cumulative incidence of mortality by cause of death was analyzed using competing risks methodology, specifically employing Fine-Gray\\u0026rsquo;s test. To assess the relative risk of BCRD and non-BCRD across different treatment groups, the sub-distribution hazard ratio (SHR) was calculated. The SHR quantifies the impact of covariates on the cumulative incidence function while accounting for competing risks, allowing for a direct comparison of the cumulative incidence of BCRD, considering the competing risk of non-breast-cancer-related deaths. The standardized mortality ratio (SMR) was determined by comparing the observed mortality in MBC patients to the expected mortality in a matched general population. Relative survival (RS) is defined as the ratio of observed survival in cancer patients to the expected survival in a comparable group from the general population. By applying a transformed Cox regression model for RS, excess mortality associated with the treatment group was assessed, accounting for population-specific risks and adjusting each patient's survival time to the corresponding expected mortality rate. Life tables and death rates used for calculating SMR and RS were sourced from U.S. population data. To assess the proportion and hazard ratio of BCRD and non-BCRD across the groups, splines were modeled with age as a continuous variable. The placement of spline knots was optimized using the C-index and Akaike Information Criterion (AIC) to ensure the best model fit. Categorical variables were compared using the chi-square test. All statistical analyses were conducted using R version 4.3.3 (R Foundation for Statistical Computing, Vienna, Austria), employing the \\u003cem\\u003etidycmprsk\\u003c/em\\u003e, \\u003cem\\u003esurvival\\u003c/em\\u003e, \\u003cem\\u003edplyr\\u003c/em\\u003e, \\u003cem\\u003emstate\\u003c/em\\u003e, \\u003cem\\u003ecmprsk\\u003c/em\\u003e, \\u003cem\\u003esurvminer\\u003c/em\\u003e, \\u003cem\\u003eriskRegression\\u003c/em\\u003e, \\u003cem\\u003ecmprskcoxmsm\\u003c/em\\u003e, and \\u003cem\\u003esplines\\u003c/em\\u003e packages. Data from the SEER database (SEER Research Data, 17 Registries, Nov 2023 Sub [2000\\u0026ndash;2021]) were retrieved using SEER*Stat software version 8.4.2.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cdiv id=\\\"Sec7\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eBaseline characteristics and treatment trend\\u003c/h2\\u003e \\u003cp\\u003eWe initially identified 9,695 MBC patients from the SEER-17 database as the study population. Following the application of exclusion criteria, 765 early-stage, low-risk patients were included, with 95 patients in the radiotherapy (RT) group and 670 in the non-radiotherapy (NRT) group. To mitigate potential selection bias and address the imbalance in sample sizes between the treatment and control groups, we conducted a 1:3 PSM. After PSM, a total of 360 patients were retained, comprising 93 in the RT group and 267 in the NRT group. Baseline characteristics before PSM are presented in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e, and the baseline characteristics after PSM are shown in Supplementary Table\\u0026nbsp;1. The median age of the entire cohort before PSM was 75 years (range, 65\\u0026ndash;90), and 73 years (range, 65\\u0026ndash;90) after PSM. Stage I disease was observed in 68.4% and 70.8% of patients before and after PSM. After PSM, the distribution of characteristics between the treatment arms was well balanced (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e(B)).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eBaseline characteristics of early-stage low-risk male breast cancer patients stratified by primary treatment (2000\\u0026ndash;2021).\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"5\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eCharacteristic\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003eAll patients\\u003c/p\\u003e \\u003cp\\u003eNo. (%)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c4\\\" namest=\\\"c3\\\"\\u003e \\u003cp\\u003eTreatment\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"1\\\" rowspan=\\\"2\\\"\\u003e \\u003cp\\u003e\\u003cem\\u003eP\\u003c/em\\u003e value\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eRT\\u003c/p\\u003e \\u003cp\\u003eNo. (%)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eNRT\\u003c/p\\u003e \\u003cp\\u003eNo. (%)\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eTotal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e765 (100)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e95 (100)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e670 (100)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e-\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAge, years\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.027\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMedian age, year (range)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e75 (65\\u0026ndash;90)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e72 (65\\u0026ndash;90)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e75 (65\\u0026ndash;90)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e65\\u0026ndash;75\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e415\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e63 (66.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e352 (52.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u0026gt;\\u0026thinsp;75\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e350\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e32 (33.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e318 (47.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eGender\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e-\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMale\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e765 (100)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e95 (100)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e670 (100)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eClinical stage\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.804\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eI\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e523 (68.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e66 (69.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e457 (68.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eII\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e242 (31.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e29 (30.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e213 (31.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003epT stage\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.804\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eT1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e523 (68.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e66 (69.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e457 (68.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eT2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e242 (31.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e29 (30.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e213 (31.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eTumor size\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.345\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMedian, mm (range)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e18.0 (1.0\\u0026ndash;30.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e17.0 (1.0\\u0026ndash;30.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e18.0 (1.0\\u0026ndash;30.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eER\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.004\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePositive\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e3 (0.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2 (2.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1 (0.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNegative\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e762 (99.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e93 (97.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e669 (99.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePR\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.605\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePositive\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e716 (93.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e90 (94.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e626 (93.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNegative\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e38 (5.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e5 (5.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e33 (4.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eUnknown\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e11 (1.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0 (0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e11 (1.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eHER2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.373\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePositive\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e31 (4.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2 (2.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e29 (4.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNegative\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e477 (62.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e59 (62.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e418 (62.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eUnknown\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e257 (33.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e34 (35.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e223 (33.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eYear of diagnosis\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.580\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2000\\u0026ndash;2005\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e111 (14.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e15 (15.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e96 (14.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2005\\u0026ndash;2010\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e172 (22.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e23 (24.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e149 (22.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2010\\u0026ndash;2015\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e238 (31.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e28 (29.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e210 (31.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e2015\\u0026ndash;2021\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e244 (31.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e29 (30.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e215 (32.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eEnd point status\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.693\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAlive\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e457 (59.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e397 (59.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e60 (63.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBreast-cancer-related death (BCRD)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e58 (7.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e55 (8.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e3 (3.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNon-BCRD\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e250 (32.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e32 (33.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e218 (32.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eRace\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.469\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eWhite\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e666 (87.1)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e81 (85.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e585 (87.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBlack\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e50 (6.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e11 (11.6)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e39 (5.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eOther\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e46 (6.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3 (3.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e43 (6.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eUnrecorded\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e3 (0.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0 (0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e3 (0.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMarital status\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.871\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMarried\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e531 (69.4)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e72 (75.8)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e459 (68.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\" morerows=\\\"3\\\" rowspan=\\\"4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDivorced/separated/widowed\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e134 (17.5)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e14 (14.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e120 (17.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSingle/unmarried/domestic partner\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e70 (9.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e5 (5.3)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e65 (9.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eUnrecorded\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e30 (3.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e4 (4.2)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e26 (3.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eThe trend of treatment among early-stage MBC patients who underwent BCS is illustrated in Supplement Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e. The proportion of patients receiving RT remained consistently low, ranging from 10\\u0026ndash;25% throughout the study period, while the proportion of patients in the NRT group increased from 70% to nearly 90% by 2020. Notably, the RT group experienced minimal fluctuations, while the NRT group saw a steady rise, particularly after 2015. This trend suggests a shift in clinical practice towards more conservative treatment approaches, possibly influenced by the treatment strategies used in female cohorts, leading to the omission of adjuvant radiotherapy after BCS.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eAbsolute overall survival analysis\\u003c/h2\\u003e \\u003cp\\u003eThe median follow-up time for the entire cohort was 103 months, with 99 months for the RT group and 106 months for the NRT group. The overall survival of the groups was not continuously separated overtime both before and after PSM adjusted (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). The unadjusted OS of 5-, 10-, 15-year were, respectively, 85.4%, 57.0% and 31.3% in RT group and 73.9%, 44.8% and 31.4% in NRT group (HR 0.78, 95%CI 0.55\\u0026ndash;1.10, \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.160; Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e(A)). The PSM-adjusted OS of 5-, 10-, 15-year were, respectively, 86.8%, 57.9% and 31.8% in RT group and 75.4%, 43.7% and 34.1% in NRT group (HR 0.83, 95%CI 0.57\\u0026ndash;1.23, \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.360; Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e(B)). To further minimize the impact of confounding factors, we performed a multivariable analysis based on Cox model. In this analysis, the use of RT had no significant effect on overall survival (HR 0.93, 95% CI 0.62\\u0026ndash;1.40; \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.73; Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e(C)).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eIn disease specific analysis, RT showed limited impact on both breast cancer related death (BCRD) and non-BCRD. The cumulative incidence of breast cancer-related death (BCRD) at 5, 10 and 15 years was 0%, 3.9%, and 6.9%, respectively, in the RT group, compared to 6.7%, 10.7%, and 12.8% in the NRT group (SHR 0.95, 95% CI 0.74\\u0026ndash;1.23, \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.06; Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e(A)), before PSM adjustment. After PSM adjustment, the cumulative incidence remained similar, with rates of 0%, 3.9%, and 7.0% in the RT group, and 8.6%, 11.1%, and 12.4% in the NRT group (SHR 0.96, 95% CI 0.74\\u0026ndash;1.23, \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.06; Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e(B)). The unadjusted cumulative incidence of non-BCRD at 5-, 10-, 15-year were, respectively, 14.6%, 39.1%, and 61.9% in RT group and 19.4%, 44.5%, and 55.8% in NRT group (SHR 0.95, 95%CI 0.88\\u0026ndash;1.28, \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.84; Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e(C)), and 13.2%, 38.2%, and 61.2% in RT group and 16.0%, 45.2%, and 53.5% in NRT group after PSM adjusted (SHR 0.87, 95%CI 0.93\\u0026ndash;1.44, \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.75; Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e(D)).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\\n\\u003ch3\\u003eNet survival impact\\u003c/h3\\u003e\\n\\u003cp\\u003eTo minimize the impact of background mortality on overall survival, we assessed the net survival benefit of RT in comparison to the general population. In early-stage, low-risk MBC patients who did not receive adjuvant RT after BCS, no significant differences were observed in standardized mortality ratios (SMR) or relative survival (RS) compared to those who received RT. After PSM, the SMR of overall survival was 2.14 in the RT group and 2.25 in the NRT group (RR 0.95, 95% CI 0.65\\u0026ndash;1.40, \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.81; Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e(A)). Since the follow-up for the RT group did not extend to 20 years, the comparison focused on RS at 5, 10, and 15 years. During the observation period, RS remained stable in both the RT and NRT groups. After PSM, the 5-, 10-, and 15-year RS in the RT group were 1.044, 1.048, and 1.047, respectively, compared to 1.070, 1.051, and 1.031 in the NRT group (HR 0.83, 95% CI 0.57\\u0026ndash;1.23, \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.35; Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e(B)).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eTo further explore the changes in dynamic radiotherapy-associated risk, we analyzed the relative risk (RR) at 5, 10, and 15 years after diagnosis. In the dynamic RR plot for BCRD (Supplement Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e(A)), the relative risk between the RT and NRT groups showed no significant increase in the RT group over time. At 5 years, the adjusted RR was 0.27 (95% CI, 0.06\\u0026ndash;1.18; \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.07), and at 10 years, the RR was 0.33 (95% CI, 0.10\\u0026ndash;1.10; \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.03). The risk remained relatively stable through 15 years, with an RR of 0.46 (95% CI, 0.39\\u0026ndash;1.26; \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.24). For non-BCRD (Supplement Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e(B)), the RT group demonstrated a stable relative risk in the early years, with an RR of 0.75 (95% CI, 0.37\\u0026ndash;1.52; \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.45) at 5 years and 0.70 (95% CI, 0.43\\u0026ndash;1.12; \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.35) at 10 years. However, by 15 years, there was an upward trend, with the adjusted RR reaching 1.20 (95% CI, 0.78\\u0026ndash;1.84; \\u003cem\\u003ep\\u003c/em\\u003e\\u0026thinsp;=\\u0026thinsp;0.68).\\u003c/p\\u003e\\n\\u003ch3\\u003eTime dependent survival evaluation\\u003c/h3\\u003e\\n\\u003cp\\u003eBased on the longitudinal assessment, the survival benefits of RT compared to non-RT group changed rapidly within the first 10 years after diagnosis (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig5\\\" class=\\\"InternalRef\\\"\\u003e5\\u003c/span\\u003e). The hazard ratios (HRs) for overall survival (OS) and relative survival (RS) changed over time, increasing from 0.658 and 0.572 at 1 year to 0.598 and 0.529 at 5 years, and further rising to 0.725 and 0.640 at 10 years, respectively. This finding underscores the necessity of a minimal 10-year follow-up to clearly identify the maximal survival differences and treatment benefits of radiotherapy compared to non-radiotherapy approaches, as demonstrated in the longitudinal data.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eWith the rising incidence of breast cancer, particularly among the aging population [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e], research is increasingly focused on treatment de-intensification for low-risk patients, such as those with low-grade, hormone receptor-positive disease [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e], to minimize treatment burden, reduce side effects, and improve quality of life. Despite the relatively lower prevalence of MBC compared to its female counterpart, recent years have seen a notable rise in its incidence, emphasizing the need of developing tailored treatment strategies for MBC in medical research and clinical practice [\\u003cspan citationid=\\\"CR31\\\" class=\\\"CitationRef\\\"\\u003e31\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR32\\\" class=\\\"CitationRef\\\"\\u003e32\\u003c/span\\u003e]. While these strategies have shown promise in FBC, it remains uncertain whether treatment de-intensification is equally applicable to MBC patients, given the unique biological and clinical characteristics of this population. Further research is required to evaluate the feasibility and outcomes of less intensive treatment approaches in MBC. Our study, utilizing data from SEER databases, evaluates the role of adjuvant radiotherapy in the management of hormone receptor-positive MBC patients aged over 65, diagnosed at an early stage (T\\u003csub\\u003e1\\u0026thinsp;\\u0026minus;\\u0026thinsp;2\\u003c/sub\\u003eN\\u003csub\\u003e0\\u003c/sub\\u003eM\\u003csub\\u003e0\\u003c/sub\\u003e), addressing the specific challenges associated with this population. Through a multi-faceted analysis involving absolute survival, net survival, and time-dependent survival, our findings suggest that radiotherapy does not confer additional survival benefits compared to its omission in early-stage low-risk MBC patients.\\u003c/p\\u003e \\u003cp\\u003eIn our study, RT use remained consistently low, while the NRT group showed a marked increase, particularly after 2015, reflecting the broader trend of radiotherapy de-escalation in breast cancer treatment. Studies like CALGB 9343 [\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e] and PRIME II [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e] have demonstrated that omitting RT in low-risk, older female patients have no adverse effect on overall survival, while maintaining satisfactory local control. These findings, along with the 2017 NCCN guidelines, which introduced recommendations for omitting RT in low-risk female patients [\\u003cspan citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e], likely contributed to the increasing trend of RT omission in MBC management.\\u003c/p\\u003e \\u003cp\\u003eIn our study involving low-risk elderly MBC patients, we found no significant differences between the RT and NRT groups in OS, RS, or disease-specific survival. The 15-year OS rate was 31.8% in the RT group compared to 34.1% in the NRT group. Even after PSM and further multivariable adjustment using Cox regression, these differences remained non-significant. These findings suggest that omitting radiotherapy may not negatively impact long-term survival in this patient cohort, aligning with the trend of treatment de-escalation observed in low-risk FBC populations. For example, both the CALGB 9343 and PRIME II studies demonstrated that in low-risk, elderly female patients, omitting radiotherapy does not negatively affect overall survival, while still maintaining satisfactory local control [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e]. This provides strong support for treatment de-escalation in low-risk breast cancer patients. However, due to the biological and clinical differences between male and female breast cancer, the applicability of this conclusion in male patients requires careful evaluation. MBC tends to have a poorer prognosis and is often more aggressive, making it less straightforward to apply treatment strategies from FBC directly to male patient [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR33\\\" class=\\\"CitationRef\\\"\\u003e33\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR34\\\" class=\\\"CitationRef\\\"\\u003e34\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eWhen discussing the impact of radiotherapy on BCRD, our findings did not show a significant reduction in risk. Similarly, results from the CALGB 9343 trial in female patients demonstrated that omitting radiotherapy had a relatively small effect on local recurrence rates in low-risk populations [\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e]. While radiotherapy may provide local control benefits in male patients, its effect on lowering breast cancer-specific mortality remains limited [\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e]. This is particularly relevant for older patients, where background mortality due to non-cancer-related factors like cardiovascular disease and other comorbidities becomes increasingly significant, reducing the potential survival benefit of radiotherapy [\\u003cspan citationid=\\\"CR35\\\" class=\\\"CitationRef\\\"\\u003e35\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR36\\\" class=\\\"CitationRef\\\"\\u003e36\\u003c/span\\u003e]. As Giordano et al. highlighted, non-cancer-related deaths often become the predominant cause of mortality in elderly breast cancer patients, stressing the need for tailored treatment strategies in elderly MBC patients [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]. These findings reinforce the importance of personalized treatment approaches, particularly when weighing the benefits of radiotherapy against the increased risk of non-cancer mortality in this patient population. Further leveraging RS and SMR as endpoints to assess treatment-related adverse events and age-related background mortality, we found no significant differences between the RT and NRT groups. Notably, between the ages of 65 and 80, the SMR curves for both groups remained stable and closely aligned. However, after age 80, particularly beyond 85, the SMR for the NRT group rose significantly. This likely reflects the increasing influence of background mortality from non-cancer-related causes in the elderly, overshadowing the effect of radiotherapy on controlling breast cancer-specific mortality [\\u003cspan citationid=\\\"CR37\\\" class=\\\"CitationRef\\\"\\u003e37\\u003c/span\\u003e]. This suggests that in older populations, non-cancer-related factors play a more dominant role in survival outcomes, highlighting the need to carefully consider the utility of radiotherapy in these cases. The RR analysis in this study further supports this finding. For BCRD, no significant differences were observed between the RT and NRT groups. However, after 10 years, non-BCRD significantly increased in the NRT group, underscoring the importance of background mortality in elderly patients. Similar results have been reported in other studies on FBC, where the cardiovascular risks tend to increase over time, potentially offsetting the long-term benefits of radiotherapy [\\u003cspan citationid=\\\"CR38\\\" class=\\\"CitationRef\\\"\\u003e38\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR39\\\" class=\\\"CitationRef\\\"\\u003e39\\u003c/span\\u003e]. After multivariable adjustment, we observed no significant differences in OS and RS between the RT and NRT groups throughout the 15-year follow-up period. Although radiotherapy appeared to confer a slight advantage in the first 10 years, this survival benefit diminished over time. This aligns with findings from some studies in female breast cancer, where the long-term impact of radiotherapy in low-risk patients has been shown to be limited, further supporting the rationale for omitting radiotherapy in certain cases [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR40\\\" class=\\\"CitationRef\\\"\\u003e40\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eDue to the limited data available on MBC, it is difficult to directly compare our results with other MBC studies, leaving us to rely on comparisons with female cohorts. Thus, caution is still needed when considering the omission of radiotherapy. At present, treatment de-intensification for elderly, low-risk patients have become a significant trend. This approach not only addresses the convenience of treatment and psychosocial factors for patients but also takes into account non-cancer-related mortality, which is particularly relevant in older populations. Current research is expanding beyond the omission of RT to consider the omission of endocrine therapy as well, given that MBC patients often show poor adherence to endocrine treatments [\\u003cspan additionalcitationids=\\\"CR42 CR43\\\" citationid=\\\"CR41\\\" class=\\\"CitationRef\\\"\\u003e41\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR44\\\" class=\\\"CitationRef\\\"\\u003e44\\u003c/span\\u003e]. However, most studies have excluded male cohorts, like the EUROPA trial [\\u003cspan citationid=\\\"CR45\\\" class=\\\"CitationRef\\\"\\u003e45\\u003c/span\\u003e], making it difficult to provide definitive information for MBC. Unfortunately, as the SEER database lacks information on endocrine therapy, we were unable to explore this aspect in our study. Although no statistically significant differences were observed between the RT and NRT groups in OS, net survival, or disease-specific survival in this study, treatment de-intensification in MBC, as emphasized in other research, should still be approached with caution.\\u003c/p\\u003e \\u003cp\\u003eThis study has some strengths. First, this study is a population-based analysis derived from a comprehensive public database, encompassing multicenter and multi-ethnic patient data, which provides robust insights into long-term survival outcomes across a diverse cohort. Second, our study employed a multifaceted analytical approach, evaluating OS, disease-specific survival, RS, SMR, and RR, offering a thorough assessment of the potential impact of radiotherapy from various perspectives. Third, PSM was used to minimize baseline differences between the RT and NRT groups, reducing potential confounding and allowing for a more accurate comparison of survival outcomes in low-risk MBC patients.\\u003c/p\\u003e \\u003cp\\u003eThis study has several limitations that should be acknowledged. First, the relatively small sample size, particularly in the RT group after PSM adjustment, may have reduced the statistical power to detect subtle differences between the groups. This is likely due to the limited use of BCS in MBC patients [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR46\\\" class=\\\"CitationRef\\\"\\u003e46\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR47\\\" class=\\\"CitationRef\\\"\\u003e47\\u003c/span\\u003e], as BCS is less common in men due to the small volume of breast tissue. In fact, only 4% \\u0026minus;\\u0026thinsp;19.8% of men with T1N0 tumors undergo BCS, which may have contributed to the low number of patients receiving adjuvant radiotherapy [\\u003cspan additionalcitationids=\\\"CR47\\\" citationid=\\\"CR46\\\" class=\\\"CitationRef\\\"\\u003e46\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR48\\\" class=\\\"CitationRef\\\"\\u003e48\\u003c/span\\u003e]. Additionally, the lack of established treatment guidelines specific to MBC may lead to variability in treatment decisions, potentially resulting in the underuse of radiotherapy. Previous studies, such as Bakalov et al., have shown that despite evidence suggesting radiotherapy can reduce mortality, a significant proportion of male BCS cases\\u0026mdash;about one-third\\u0026mdash;did not receive adjuvant RT [\\u003cspan citationid=\\\"CR49\\\" class=\\\"CitationRef\\\"\\u003e49\\u003c/span\\u003e]. This variability has increased the difficulty in obtaining relevant data for the RT group and further complicates the evaluation of RT's impact in this cohort. Second, the data derived from the SEER database may limit access to certain clinical details, such as radiotherapy fractionation, chemotherapy regimens and cycles, as well as endocrine therapy information. This lack of granularity restricts our ability to further analyze the relationship between treatment factors and survival outcomes. Third, as an observational retrospective study, it is challenging to control for residual confounding factors that may influence treatment outcomes, and thus, the conclusions drawn from this study require validation through larger randomized controlled trials.\\u003c/p\\u003e \\u003cp\\u003eIn conclusion, radiotherapy did not confer a significant survival benefit in MBC patients over 65 with T1-2N0M0, hormone receptor-positive tumors. Further randomized controlled trials are warranted to confirm these findings, with particular attention to the role of endocrine therapy. Despite the rarity of MBC, prospective studies remain essential to fully evaluate the long-term risks and benefits of radiotherapy in this patient population.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003ch2\\u003eAuthor Contribution\\u003c/h2\\u003e\\u003cp\\u003eChang Xu: Conceptualization, Methodology, Formal analysis, Writing - Original DraftCheng Zeng: Methodology, Formal analysis,Writing - Original DraftHanheng Meng: Project administration, Writing - Review \\u0026amp; EditingFei Ma: Supervision, Validation, Writing - Review \\u0026amp; Editing\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eLin AP, Huang TW, Tam KW (2021) Treatment of male breast cancer: meta-analysis of real-world evidence. 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Breast 38:154\\u0026ndash;159\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKunkler IH, Williams LJ, Jack WJL, Cameron DA, Dixon JM (2023) Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer. N Engl J Med 388(7):585\\u0026ndash;594\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKunkler IH, Williams LJ, Jack WJL, Cameron DA, Dixon JM (2015) Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol 16(3):266\\u0026ndash;273\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSlamon D, Lipatov O, Nowecki Z, McAndrew N, Kukielka-Budny B, Stroyakovskiy D, Yardley DA, Huang C-S, Fasching PA, Crown J et al (2024) Ribociclib plus Endocrine Therapy in Early Breast Cancer. N Engl J Med 390(12):1080\\u0026ndash;1091\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eReinisch M, Seiler S, Hauzenberger T, Kamischke A, Schmatloch S, Strittmatter H-J, Zahm D-M, Thode C, Furlanetto J, Strik D et al (2021) Efficacy of Endocrine Therapy for the Treatment of Breast Cancer in Men: Results from the MALE Phase 2 Randomized Clinical Trial. JAMA Oncol 7(4):565\\u0026ndash;572\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eArslan UY, Oks\\u0026uuml;zoğlu B, Ozdemir N, Aksoy S, Alkış N, G\\u0026ouml;k A, Kaplan MA, G\\u0026uuml;m\\u0026uuml;ş M, Berk V, Uncu D et al (2012) Outcome of non-metastatic male breast cancer: 118 patients. Med Oncol 29(2):554\\u0026ndash;560\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eFouhi ME, Mesfioui A, Benider A (2020) Male breast cancer: a report of 25 cases. 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Lancet Oncol 22(7):e327\\u0026ndash;e340\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, Muss HB, Smith BL, Hudis CA, Winer EP et al (2013) Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol 31(19):2382\\u0026ndash;2387\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eReddington R, Galer M, Hagedorn A, Liu P, Barrack S, Husain E, Sharma R, Speirs V, Masannat Y (2020) Incidence of male breast cancer in Scotland over a twenty-five-year period (1992\\u0026ndash;2017). Eur J Surg Oncol 46(8):1546\\u0026ndash;1550\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMukherjee AG, Gopalakrishnan AV, Jayaraj R, Renu K, Dey A, Vellingiri B, Malik T (2023) The incidence of male breast cancer: from fiction to reality - correspondence. Int J Surg 109(9):2855\\u0026ndash;2858\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGwark S, Kim J, Chung IY, Kim HJ, Ko BS, Lee JW, Son BH, Ahn SH, Lee SB (2024) Survival pattern in male breast cancer: distinct from female breast cancer. Front Oncol 14:1392592\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGnerlich JL, Deshpande AD, Jeffe DB, Seelam S, Kimbuende E, Margenthaler JA (2011) Poorer survival outcomes for male breast cancer compared with female breast cancer may be attributable to in-stage migration. Ann Surg Oncol 18(7):1837\\u0026ndash;1844\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eJ\\u0026oslash;rgensen TL, Hallas J, Friis S, Herrstedt J (2012) Comorbidity in elderly cancer patients in relation to overall and cancer-specific mortality. Br J Cancer 106(7):1353\\u0026ndash;1360\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ede Glas NA, Kiderlen M, Vandenbroucke JP, de Craen AJM, Portielje JEA, van de Velde CJH, Liefers G-J, Bastiaannet E, Le Cessie S (2016) Performing Survival Analyses in the Presence of Competing Risks: A Clinical Example in Older Breast Cancer Patients. J Natl Cancer Inst 108(5)\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eYang P, Zheng Y, Chen J, Ma H, Yu K, Chen Y, Yang Y, Wu B (2021) Immediate risk of non-cancer deaths after a cancer diagnosis. BMC Cancer 21(1):963\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHooning MJ, Botma A, Aleman BMP, Baaijens MHA, Bartelink H, Klijn JGM, Taylor CW, van Leeuwen FE (2007) Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst 99(5):365\\u0026ndash;375\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBouchardy C, Rapiti E, Usel M, Majno SB, Vlastos G, Benhamou S, Miralbell R, Neyroud-Caspar I, Verkooijen HM, Vinh-Hung V (2010) Excess of cardiovascular mortality among node-negative breast cancer patients irradiated for inner-quadrant tumors. Ann Oncol 21(3):459\\u0026ndash;465\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eWhelan TJ, Smith S, Parpia S, Fyles AW, Bane A, Liu F-F, Rakovitch E, Chang L, Stevens C, Bowen J et al (2023) Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer. N Engl J Med 389(7):612\\u0026ndash;619\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDemissie S, Silliman RA, Lash TL (2001) Adjuvant tamoxifen: predictors of use, side effects, and discontinuation in older women. J Clin Oncol 19(2):322\\u0026ndash;328\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePemmaraju N, Munsell MF, Hortobagyi GN, Giordano SH (2012) Retrospective review of male breast cancer patients: analysis of tamoxifen-related side-effects. Ann Oncol 23(6):1471\\u0026ndash;1474\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eVenigalla S, Carmona R, Guttmann DM, Jain V, Freedman GM, Clark AS, Shabason JE (2018) Use and Effectiveness of Adjuvant Endocrine Therapy for Hormone Receptor-Positive Breast Cancer in Men. JAMA Oncol 4(10):e181114\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eAnelli TF, Anelli A, Tran KN, Lebwohl DE, Borgen PI (1994) Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients. Cancer 74(1):74\\u0026ndash;77\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMeattini I, Poortmans PMP, Marrazzo L, Desideri I, Brain E, Hamaker M, Lambertini M, Miccinesi G, Russell N, Saieva C et al (2021) Exclusive endocrine therapy or partial breast irradiation for women aged\\u0026thinsp;\\u0026ge;\\u0026thinsp;70 years with luminal A-like early stage breast cancer (NCT04134598 - EUROPA): Proof of concept of a randomized controlled trial comparing health related quality of life by patient reported outcome measures. J Geriatr Oncol 12(2):182\\u0026ndash;189\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eChichura A, Attai DJ, Kuchta K, Nicholson K, Kopkash K, Pesce C, Yao K (2022) Male Breast Cancer Patient and Surgeon Experience: The Male WhySurg Study. Ann Surg Oncol 29(10):6115\\u0026ndash;6131\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eElmi M, Sequeira S, Azin A, Elnahas A, McCready DR, Cil TD (2018) Evolving surgical treatment decisions for male breast cancer: an analysis of the National Surgical Quality Improvement Program (NSQIP) database. Breast Cancer Res Treat 171(2):427\\u0026ndash;434\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLeone JP, Leone J, Zwenger AO, Iturbe J, Leone BA, Vallejo CT (2017) Locoregional treatment and overall survival of men with T1a,b,cN0M0 breast cancer: A population-based study. Eur J Cancer 71\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBakalov V, Jayakrishnan TT, Abel S, Hilton C, Rusia B, Wegner RE (2021) The use of adjuvant radiation therapy in male breast cancer and its impact on outcomes. Cancer Treat Res Commun 27:100359\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"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, Adjuvant radiotherapy, Breast conserving surgery, Systemic therapy, SEER\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-5285916/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-5285916/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eBackground\\u003c/h2\\u003e \\u003cp\\u003eThe aim of our study is to evaluate the net survival benefit of adjuvant radiotherapy following breast-conserving surgery (BCS) in elderly male patients with early-stage, low-risk breast cancer (node-negative, hormone receptor-positive [HR+]) and to assess whether omitting radiotherapy might be a viable option based on observed survival outcomes.\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e \\u003cp\\u003eWe conducted a retrospective cohort study using data from SEER-17 registries (2000\\u0026ndash;2021), identifying 9,695 male breast cancer (MBC) patients. After applying inclusion criteria and PSM, a total of 360 patients were included. Early-stage, low-risk patients were categorized into radiotherapy (RT) and non-radiotherapy (NRT) groups. A 1:3 nearest neighbor propensity score matching (PSM; caliper\\u0026thinsp;=\\u0026thinsp;0.05) was used to adjust for confounders. Estimate the net survival benefit of RT by using overall survival (OS), relative survival (RS), standardized mortality ratio (SMR), and transformed Cox regression, while controlling for background mortality.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003eIn early-stage, low-risk MBC patients underwent BCS, RT did not confer a significant survival benifit compared to those who omitted RT. After PSM adjustment, the 15-year OS, RS, and SMR for the RT group were 31.8%, 1.05, and 2.14, respectively, with no statistically significant differences observed when compared to the NRT group (34.1%, 1.03, and 2.25; p\\u0026thinsp;=\\u0026thinsp;0.36, 0.35, and 0.81, respectively). Furthermore, the cumulative incidence of breast cancer-related death (BCRD) and non-BCRD did not differ significantly between the RT and NRT groups. The 15-year cumulative incidences of BCRD and non-BCRD were 7.0% and 61.2% in the RT group, and 12.4% and 53.5% in the NRT group (p\\u0026thinsp;=\\u0026thinsp;0.06 and 0.75, respectively). Additionally, compared to the NRT group, the RT group demonstrated a lower risk for both OS and RS within the first 10 years following diagnosis, although this survival benefits gradually diminished over time.\\u003c/p\\u003e\\u003ch2\\u003eConclusions\\u003c/h2\\u003e \\u003cp\\u003eIn MBC patients over 65 with T\\u003csub\\u003e1\\u0026thinsp;\\u0026minus;\\u0026thinsp;2\\u003c/sub\\u003eN\\u003csub\\u003e0\\u003c/sub\\u003eM\\u003csub\\u003e0\\u003c/sub\\u003e, hormone receptor-positive tumors, radiotherapy showed no significant improvement in overall, disease-specific, or net survival. Therefore, omitting radiotherapy may be justified for early-stage, low-risk patients, aligning treatment with individualized risk assessments.\\u003c/p\\u003e\",\"manuscriptTitle\":\"The Role of Adjuvant Radiotherapy in Low-Risk Elderly Male Breast Cancer: Is Omission Justified?\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-10-23 10:46:40\",\"doi\":\"10.21203/rs.3.rs-5285916/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"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\":\"02985a12-ad43-46be-bfe6-7721b81b82f6\",\"owner\":[],\"postedDate\":\"October 23rd, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-11-08T14:39:00+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-10-23 10:46:40\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-5285916\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-5285916\",\"identity\":\"rs-5285916\",\"version\":[\"v1\"]},\"buildId\":\"-D5TCW68w8eVRRLyjaTIo\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}