Abstract Background: Estrogen receptor-positive (ER+) breast cancer is the most commonly diagnosed subtype in both male and female patients. However, due to the rarity of male breast cancer overall, there remains limited understanding of how this specific subtype is treated and how outcomes compare between sexes. This study aims to compare survival and contemporary treatment for ER+ male breast cancer (MBC) and female breast cancer (FBC) patients within the Veterans Health Administration (VHA). Methods: We conducted a retrospective cohort study of patients diagnosed with ER+ MBC and FBC between 2000 and 2020 using national data from the VHA Informatics and Computing Infrastructure database. Demographics, tumor characteristics, treatment (surgery, chemotherapy, radiation), and survival were compared between MBC and FBC patients. Stage 0 and IV patients were excluded from our analysis. Descriptive statistics, t-tests, and chi-square tests were used to compare the cohorts. Cox proportional hazards regression models were utilized to examine overall survival, controlling for age, race, body mass index, and grade. Results: Of the 6,336 total patients identified, 17.9% (n=1,134) were male. ER+ MBC patients were 66.0% White (n=754), 23.0% Black (n=257), and 11.0% Other/Unknown race (n=123). Most ER+ MBC patients were Non-Hispanic (n=1024, 90.0%). The average BMI of ER+ MBC patients was 30.6. ER+ MBC patients were significantly more likely to be diagnosed at an older age (69.0 vs. 57.7, p 0.001). Significantly more MBC patients were diagnosed with stage II (46.5% vs. 33.2%, p 0.001) and stage III disease (20.9% vs. 10.1%, p 0.001) than FBC. Compared to ER+ FBC patients, MBC patients had significantly higher rates of ductal histology (87.0% vs. 82.0%, p 0.001), grade 2 disease (39.0% vs 32.0%, p 0.001), and grade 3 disease (24% vs. 17.0%, p 0.001). MBC and FBC ER+ patients had similar rates of undergoing surgery (MBC: 94.0% vs. FBC: 96.0%) and chemotherapy (40.0% vs. 43.3%). Significantly more ER+ FBC patients underwent radiation therapy than MBC patients (53.0% vs. 23.0%, p 0.001). In a Cox proportional hazard model, stage I (HR 1.41, 95% CI: 1.06-1.86) and stage II (HR 2.06, 95% CI: 1.64-2.58) ER+ MBC patients had significantly higher risk-adjusted hazard of all-cause mortality when compared to FBC patients. Conclusions: Despite receiving similar surgical and chemotherapy treatments, ER+ MBC were more often diagnosed at later stages and had significantly worse risk-adjusted survival compared to ER+ FBC. These findings highlight the need for increased awareness, earlier detection, and tailored treatment strategies for ER+ MBC patients. Citation Format: A. Naaseh, J. B. Gruber, R. L. Aft, K. N. Maxwell, M. W. Schoen. Sex-based differences in hormone receptor-positive breast cancer treatment and outcomes: A Veterans Health Administration 20-year cohort study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-08-20.
Naaseh et al. (2026) studied this question.