Patterns of recurrence and metastasis in BRCA1/BRCA2-associated breast cancers

Breast cancer subtypes are associated with distinct metastatic patterns. Whether germline BRCA1/BRCA2 mutation status is independently associated with central nervous system (CNS) relapse, controlling for tumor subtype, is unknown.

Patients who were treated at Dana-Farber Cancer Institute and diagnosed with a first locoregional recurrence (LRR) or metastasis between 1981 and 2014 were identified using 2 institutional registries: 1) patients treated for recurrent breast cancer and 2) patients who underwent BRCA testing. The frequencies of LRR, sites of metastasis, and breast cancer-specific survival from LRR or metastasis were calculated, and the factors associated with CNS recurrence were evaluated using multivariable logistic regression models.

The final study cohort included 30 BRCA1 mutation carriers, 32 BRCA2 mutation carriers, and 270 noncarriers. Most BRCA1 carriers (73%) had triple-negative breast cancer; whereas most BRCA2 carriers (72%) had hormone receptor-positive tumors. BRCA1 carriers frequently experienced lung and distant lymph node metastasis, whereas BRCA2 carriers and noncarriers most often experienced bone metastasis. Although CNS disease occurred frequently in both BRCA1 and BRCA2 carriers (53% BRCA1, 50% BRCA2, 25% noncarriers; P < .001), only BRCA2 mutation (P = .006) was significantly associated with CNS metastasis in multivariable analysis controlling for tumor subtype. BRCA2 mutation (P = .01), triple-negative subtype (P < .001), and the involvement of CNS (P < .001) and other non-CNS distant sites (relative to locoregional recurrence or contralateral disease; P < .001) at presentation of recurrent breast cancer were associated with risk for mortality.

CNS involvement is frequent in women with germline BRCA1/BRCA2 mutations who have metastatic breast cancer. BRCA2 mutation carriers had a significantly higher frequency of CNS metastasis than noncarriers when controlling for breast cancer subtype.