Abstract Background: Approximately 13% of all breast cancers (BC) in men are HER2 positive. Previous studies have suggested that men with HER2-positive BC have worse prognosis compared to women with HER2-positive disease. Despite advances in HER2-positive BC treatment over recent years, it remains unclear whether mortality rates have decreased in men as they have in women. The aims of this study were to compare breast cancer-specific mortality (BCSM) between men and women with HER2-positive BC and evaluate changes in BCSM in each sex over time. Methods: We evaluated men and women diagnosed with HER2-positive invasive BC between 2010 and 2022, reported in the Surveillance, Epidemiology, and End Results registry. Patients were categorized into two groups by year of diagnosis: 2010-2015, and 2016-2022. BCSM was estimated by cumulative incidence function and differences between groups were compared by Gray’s test. Fine and Gray model was used to evaluate differences in BCSM between men and women after adjusting for age, year of diagnosis, race, ethnicity, tumor grade, tumor histology, hormone receptor status, tumor stage, surgery type, chemotherapy, radiation, marital status, income, rurality, and region of residence. Stratified adjusted Fine and Gray models were fitted for each sex to assess whether there was an association between year of diagnosis and BCSM. For all analyses of BCSM, deaths from causes other than BC were treated as a competing event. Results: We included 483 men (2010-2015: N = 189, 2016-2022: N = 294) and 85,693 women (2010-2015: N = 36,578, 2016-2022: N = 49,115) diagnosed with HER2-positive BC. Comparing men vs women in the overall population, men were older (median age 62 vs 57 years), more often non-Hispanic white (68% vs 58%), presented more often with de-novo stage IV (14.7% vs 9.2%) and with hormone receptor positive BC (94.4% vs 69.7%), respectively (p0.001 for each). The median follow-up for patients diagnosed 2010-2015 was 9.4 years in men and 9.5 years in women; for patients diagnosed 2016-2022 was 3.4 years in men and 3.3 years in women. Overall, BCSM at 5 years was 19.8% in men vs 11.6% in women, p0.001. Men had higher risk of BCSM than women in the adjusted Fine and Gray model (adjusted subdistribution hazard ratio aSHR, 1.3; 95% CI, 1.02-1.68). Among men, BCSM at 5 years was 20.0% and 20.5% in periods 2010-2015 and 2016-2022, respectively; p=0.9. In women, BCSM at 5 years was 12.5% in 2010-2015 and 10.4% in 2016-2022, p0.001. In adjusted Fine and Gray models evaluating year of diagnosis as a continuous variable, each successive year of diagnosis had no significant association with BCSM in men (aSHR, 0.99; 95% CI, 0.91-1.08; p=0.9), but a significant association with BCSM in women (aSHR, 0.97; 95% CI, 0.96-0.98; p0.001). Analysis of overall survival (OS) showed that men had significantly worse OS than women (5-year OS rate 65.3% vs 84.1%, respectively; p0.001). Men had no significant differences in OS for those diagnosed 2010-2015 vs 2016-2022 (5-year OS rate 64.4% vs 64.7%, respectively; p=0.6). 5-year OS rate in women was 83.4% in 2010-2015 vs 85.1% in 2016-2022; p0.001. Exploratory analyses revealed no significant improvement in BCSM across the two diagnosis periods in men with stage I-III and men with stage IV BC, whereas women had significant improvement in BCSM in both. Women showed improvements in BCSM in both the HR+/HER2+ and HR-/HER2+ subgroups, while men did not show any improvements. Conclusions: Men with HER2-positive BC exhibit significantly worse BCSM compared to women. Since 2010, BCSM has not improved in men with HER2-positive disease, contrasting with the observed reductions in BCSM among women. The lack of survival improvement in men with HER2-positive BC over time, coupled with the persistent higher mortality risk, underscores the substantial unmet medical needs for this population. Citation Format: J. P. Leone, D. Trapani, M. J. Hassett, D. L. Abravanel, P. M. Spanheimer, R. A. Freedman, C. T. Vallejo, S. M. Tolaney, N. U. Lin, J. Leone. Mortality in HER2-positive male breast cancer between 2010 and 2022: A population-based 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 PS2-13-13.
Leone et al. (Tue,) studied this question.