Brain metastasis in patients with hereditary BRCA-mutated invasive breast cancer.

Abstract

1074 Background: In the past six months, two poly(ADP-ribose) polymerase (PARP) inhibitors have been approved for the treatment of patients with metastatic breast cancer and germline pathogenic variants in BRCA1 or BRCA2 ( gBRCA). In addition, recent data from the IMpassion 130 trial lends support for the role of immunotherapy in a subset of patients with triple negative breast cancer (TNBC). Approximately 60% of patients with gBRCA1 have TNBC. There is evidence that both PARP inhibitors and checkpoint inhibitors cross the blood-brain barrier and both classes of agents have entered clinical trials for patients with brain metastases in other tumor types. We studied the clinical course of breast cancer patients with gBRCA and brain metastasis at our institution to inform clinical trial design for this group of patients with poor outcomes. Methods: Patients with stage I to III invasive breast cancer, gBRCA, and eventual development of brain metastasis were identified from clinical databases. Data analyzed included breast cancer subtype and stage at diagnosis, treatment, time to distant recurrence and to discovery of brain metastasis, and overall survival from time of development of brain metastasis. Results: Patients in our cohort (n = 24, to date) were diagnosed at a young age (median age 39) and primarily had TNBC (21/24, 87.5%) with infiltrating ductal carcinoma histology. Nineteen patients had gBRCA1 and 4 patients had gBRCA2. All but 1 patient received anthracycline-based chemotherapy in the neoadjuvant/adjuvant setting. Median time to distant metastasis was 2 years (range: 0.8 – 15) and the brain was the first site of recurrence in 5 of 24 (21%) patients. Median time from diagnosis to development of brain metastasis was 2.6 years (range: 1.2 – 19) and most patients (18/25, 72%) had multiple brain metastases discovered on the initial brain MRI. Median overall survival (OS) was 3.7 years (range: 1.8 – 24) and median OS from the time of brain metastasis was 7 months (range: 1 month – 13 years). Conclusions: Breast cancer patients with germline pathogenic variants in BRCA1/2 who develop brain metastasis have a dismal prognosis. These patients may benefit from an agent with intracranial activity at the time of first distant recurrence.