The Role of Adjuvant Radiotherapy in Low-Risk Elderly Male Breast Cancer: Is Omission Justified?

doi:10.21203/rs.3.rs-5285916/v1

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Research Article

The Role of Adjuvant Radiotherapy in Low-Risk Elderly Male Breast Cancer: Is Omission Justified?

https://doi.org/10.21203/rs.3.rs-5285916/v1

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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 − 2N₀M₀, 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

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.

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.

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
Characteristic	All patients No. (%)	RT No. (%)	NRT No. (%)	P value
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.

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 − 2N₀M₀), 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.

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

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The Role of Adjuvant Radiotherapy in Low-Risk Elderly Male Breast Cancer: Is Omission Justified?

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Baseline characteristics and treatment trend

Absolute overall survival analysis

Net survival impact

Time dependent survival evaluation

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