The incidence and impact of brain metastasis in patients with hereditary BRCA1/2 mutated invasive breast cancer in a prospectively followed cohort.

1096 Background: Previous reports suggest the incidence of brain metastasis is higher in patients with hereditary BRCA1 mutations compared to BRCA1 noncarriers among breast cancer patients who develop recurrent disease. PARP inhibitors are now standard therapies for metastatic breast cancer patients with germline BRCA1 or BRCA2 mutations ( gBRCA1/2) based on their efficacy in treating systemic disease. However, as management of systemic disease improves, a concern is that patients with hereditary BRCA mutations may experience higher rates of disease progression in the CNS. We aimed to estimate the incidence of brain metastasis in breast cancer patients with gBRCA1/2 using a prospectively maintained gBRCA database and to assess the impact of brain metastasis on survival. Methods: To determine incidence, we queried a prospectively maintained electronic database that included patients referred to the MDACC genetics department and who underwent gBRCA1/2 testing. We identified patients with stage I-III invasive breast cancer who were treated between 2000-2017 and assessed for disease recurrence and brain metastasis. To expand our cohort for descriptive characteristics (separate from the incidence analysis), we queried the Breast Medical Oncology database for patients with brain metastasis who had undergone BRCA1/2 testing outside the genetics department or at outside institutions. Results: Of 474 patients with Stage I-III breast cancer and gBRCA1, 77 (16.2%) developed distant metastasis (median f/u: 9.1 years). Of these patients, 34/77 (44.2%) developed brain metastasis. In comparison, 42 of 318 (13.2%) of gBRCA2 patients with Stage I-III breast cancer developed distant recurrence (median f/u: 8.4 years), and 7/42 (16.7%) experienced brain metastasis. In gBRCA1 patients with brain metastasis, 45/48 (83.8%) had triple negative disease, and the median time from diagnosis to brain metastasis was 2.45 years. The brain was among the initial sites of disease recurrence in 24/48 (50%) of gBRCA1 patients. For gBRCA1 patients with distantly recurrent disease, median OS from diagnosis was 3.19 years for patients with brain metastasis vs. 5.37 years for patients without brain mets (HR 0.54; 95% CI 0.34 to 0.85; P = 0.0082). Conclusions: Brain metastasis is frequent among breast cancer patients with recurrent disease and hereditary BRCA1 mutations. Development and testing of agents with intracranial activity is critical for improving long-term outcomes in gBRCA1 patients with metastatic breast cancer.