Abstract
BACKGROUND: Although BRCA1 and BRCA2 mutations are known to be associated with different breast cancer (BC) subtypes, real-world evidence on how these genetic differences influence tumor behavior and treatment decisions remains limited, particularly in Japanese patients. With the recent expansion of PARP inhibitor indications in Japan, BRCA testing has become increasingly routine, highlighting the need for clinical data tailored to local populations. OBJECTIVES: To compare clinicopathological features, recurrence patterns, and surgical choices between BRCA1- and BRCA2-associated BC in Japanese patients, with a focus on ER-positive tumors. DESIGN: A single-institution retrospective cohort study. METHODS: We retrospectively reviewed 417 patients who underwent BRCA1/2 genetic testing at a single Japanese institution between April 2020 and November 2023. Of these, 38 patients (12 BRCA1, 26 BRCA2) had pathogenic variants. We compared clinicopathological features, recurrence patterns, and choices of risk-reducing surgery between BRCA1 and BRCA2 carriers. RESULTS: BRCA1-associated cancers were predominantly triple-negative (75%) and diagnosed at earlier stages (T1 in 83.3%), while BRCA2-associated cancers were mainly ER-positive (69.2%) and more likely to present with multiple lymph node metastases (⩾2 nodes in 42.3%). Although Ki-67 levels were higher in BRCA1 tumors, this was largely subtype-dependent. Notably, ER-positive BRCA tumors showed a trend toward higher recurrence. Preferences for prophylactic surgery also varied by mutation type. CONCLUSION: This single-institution study highlights clinically meaningful differences between BRCA1- and BRCA2-associated BC in Japanese patients. BRCA2 cancers tended to present with more advanced features, while BRCA1 cancers were more often detected at earlier stage. These findings underscore the value of BRCA testing not only for PARP inhibitor eligibility but also for subtype-specific risk assessment and individualized preventive strategies.