Patterns of metastasis according to germline BRCA1/2 mutation status in patients with HER2-negative metastatic breast cancer

BRCA1/2 pathogenic variants (PVs) may influence metastatic dissemination in breast cancer (BC), but existing data are often confounded by differences in subtype distribution among carriers. We assessed associations between germline BRCA1/2 status and metastatic sites in HER2-negative BC. Patients treated for HER2-negative metastatic BC (2007–2025) with known BRCA1/2 mutation status were identified. Metastatic sites at diagnosis and throughout the disease history were collected. CNS involvement included brain metastases and/or leptomeningeal involvement. Among 184 patients (33 BRCA1 , 28 BRCA2 , 123 noncarriers), 131 presented a HR + BC and 53 a triple negative BC (TNBC). In HR + BC, BRCA1/2 carriers presented less frequently bone metastases at first metastatic diagnosis (31.4% vs. 51.0%; p = 0.046). At a median follow-up of 80.7 months, among patients with HR + BC, BRCA1/2 carriers more frequently presented CNS involvement compared to noncarriers (31.4% vs. 14.6%, p = 0.030), with an earlier onset (24-month incidence: 23.4% vs. 5.2%; p = 0.041). In TNBC, BRCA1/2 carriers presented less frequently liver metastases (34.6% vs. 70.4%, p = 0.009), with similar CNS involvement (57.7% vs. 37%, p = 0.219). Germline BRCA1/2 PVs are associated with distinct metastatic patterns, including a higher and earlier risk of CNS involvement in HR + BCs. These findings may inform tailored radiological surveillance strategies.