61P - Clinical implication of BRCA mutation in breast cancer with central nervous system metastasis

Background

Clinical implication of BRCA mutation in patients with breast cancer (BC) with central nervous system (CNS) metastasis is unclear.

Methods

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.

Results

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).

Conclusions

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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.