Clinical implication of BRCA mutation in patients with breast cancer (BC) with central nervous system (CNS) metastasis is unclear.
Data of 2,883 patients with BC who underwent BRCA1/2 mutation test at Asan Medical Center between 2011 and 2018 were reviewed. Clinical characteristics and outcomes were compared according to the presence of BRCA1/2 mutation in patients with BC with CNS metastasis.
Among 2,883 patients, 82 patients developed CNS metastasis: 29 of 696 (4.2%) in BRCA1/2 mutation carriers and 53 of 2,187 (2.4%) in non-BRCA mutation carriers. Median age at CNS metastasis was 41 yrs (range 27-76). The proportion of BC subtypes was different according to the presence of BRCA1/2 mutation: hormone receptor (HR) (+) and HER2 (-) (41.4% vs. 24.5%, P=0.113) and HER2 (+) regardless of HR (6.9% vs. 32.1%, P=0.013) between BRCA1/2 mutation and non-BRCA mutation carriers, while no difference was observed regarding triple-negative BC (TNBC) (51.7% vs. 43.4%) (P=0.470). Among patients with BRCA1/2 mutation, most of the BRCA1 mutation carriers had TNBC (77.8%), whereas most of BRCA2 mutation carriers had HR+ BC (60%) (P=0.060). Median time to CNS metastasis from metastatic BC was 1.1 yrs (95% confidence interval 0.74-1.41) without difference between BRCA1/2 and non-BRCA mutation carriers. BRCA1 carriers significantly develop CNS metastasis earlier than BRCA2 mutation carriers (0.8 vs. 1.6 yrs, P=0.015). Patterns of CNS metastasis were similar by presence of BRCA1/2 mutation: brain parenchymal metastasis (BM) alone (62.1% vs. 73.6%), leptomeningeal metastasis alone (10.3% vs. 9.4%), and both (27.6% vs. 17%). There were no differences in isolated CNS metastasis, single or multiple BM, and uncontrolled CNS metastasis rates with similar treatment of CNS metastasis. At a median follow-up of 24.5 months, median overall survival from CNS metastasis in BRCA1/2 mutation carriers seemed to be shorter than in non-BRCA mutation carriers (6.0 vs. 8.9 months, P=0.284).
CNS involvement is frequent in BRCA1/2 mutated BC and BC subtypes were different according to the presence of BRCA1/2 mutation in patients with BC with CNS metastasis. BRCA1 carriers developed CNS metastasis earlier and may be associated with poor survival.
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