Abstract Male Breast Cancer: Genomic Landscape, Epidemiological Patterns, and Clinical Outcomes in The United States Background: Male breast cancer is a rare form of breast cancer that has its distinct biological characteristics. Because of the disease rarity, most data on genomic landscape, epidemiological patterns, and clinical outcomes originate from small studies with limited number of patients. In this study, we aimed to leverage the publicly available genomic and epidemiological datasets to provide the largest to date analysis of clinic-genomic characteristics of male breast cancer in the United States. Methods: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to extract data on patients diagnosed with male breast cancer from the SEER 17 Reg. Nov 2024 submission dataset (including patients diagnosed 2000-2022). SEER collects cancer incidence data from population-based cancer registries covering approximately 45.9 percent of the U.S. population. We used the AACR project GENIE v17.0 database to extract data on genomics of patients with male breast cancer who had samples sequenced and results accessible as part of AACR project GENIE. To avoid duplication, only patients with one profiled sample were included in the analysis. Only genes which were sequenced in at least 50 samples were included in frequency calculations. Results: The epidemiology analysis set included 10,284 patients with male breast cancer. The median age was 68 (interquartile range, 18). Most patients were white (80.3%, n=8,256) and non-Hispanic non-Latino (92.7%, n=9,529). Almost 51.7% (n=5,314) had left-sided breast cancer. In patients with known receptor status, the majority had ER-positive (96.2%, n=8,908), PR-positive (88.2%, n=8,063), and HER2 negative disease (88.1%, n=5,218). Most cases had HR+/HER2- disease subtype (85.9%, n=5,073). Lower proportions had HR+/HER2+, HR-/HER-, or HR-/HER2+ disease (11.2%, n=662; 2.2%, n=128; and 0.8%, n=41; respectively). The age-adjusted incidence rate was 1.2 per 100,000 and the median OS in the overall cohort was 109 months (95% CI: 105.1-112.9).The genomic analysis set included 144 patients. The most frequently mutated genes were PIK3CA (38.2%, n=55/144), GATA3 (21.6%, n=29/134 profiled), KMT2C (14.1%, n=14/99), TP53 (13.9%, n=20/144), and BRCA2 (10.4%, n=14/135). Structural variants were most frequently observed in INPPL1 (3.4%, n=2/58), CDK12 (1.7%, n=2/121), FGFR2 (1.6%, n=2/128), FGFR1 (1.6%, n=2/128), and NSD3 genes (1.2%, n=1/81). The most frequent copy number alterations were amplifications in FGF19 (19.4%, n=14/72), FGF4 (19.4%, n=14/72), FGF3 (19.4%, n=14/72), CCND1 (17.8%, n=18/101), and FGFR1 (14.9%, n=15/101). Conclusions: Male breast cancer occurs at a rate of 1.2 per 100,000 and has a median OS of 9 years. Patients mostly present with ER+ HER- disease and a molecular profile is quite different from female breast cancer. Citation Format: l. kamal, E. Belal, a. Beddah, H. Shaheen. Male Breast Cancer: Genomic Landscape, Epidemiological Patterns, and Clinical Outcomes in The United States 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 PS3-03-01.
kamal et al. (2026) studied this question.