Evaluation of BRCA mutation (BRCAm) testing patterns, clinical characteristics and overall survival (OS) in breast cancer (BC) patients over a 20-year period

Abstract

Background: BRCAm are implicated in 5% of BC. Since PARP inhibitors may be preferentially active in BRCAm carriers with BC, we evaluated historical BRCAm testing patterns, clinical characteristics, and OS in BC patients stratified by BRCAm status. Methods: Patients with BC treated at the University of Utah Huntsman Cancer Institute (HCI) from 1995-2014 were identified from an institutional tumor registry linked to the Enterprise Data Warehouse. Germline BRCAm status was ascertained by chart review. Univariate COX regression models evaluated relationships between BRCAm and OS from BC diagnosis. Results: Study had 5712 BC patients with BRCAm testing reported in 918 (16.1%). Testing increased from 4.7% in 1995-1999 to 26.2% in 2010-2014, p < 0.001. A total of 153 (16.7%) were BRCAm+ (BRCA1 [n = 64, 41.8%], BRCA2 [n = 78, 51.0%], BRCA1 and BRCA2 [n = 2, 1.3%], and specific BRCAm not reported in 5.9% [n = 9]) and 765 were BRCAm-. Median age at BC diagnosis was 47 and 48 years in BRCAm+ and BRCAm- patients. Of those with known date of testing (n = 590, 64%), BRCA testing was conducted before BC diagnosis in 6.3% (n = 37; [more BRCAm+ vs BRCAm-, 13.3% vs 4.9%, p = 0.012]), within 90 days in 48.5% (n = 286), and ? 90 days post BC diagnosis in 45.3% (n = 267). No differences between groups were observed in ethnicity or stage at diagnosis. Triple negative BC (TNBC) was more common in BRCAm+ patients (24%, n = 36 vs 9%, n = 66; p < 0.001) and more common in BRCA1 (n = 24, 66.7%) vs BRCA2 (n = 10, 27.8%), p = 0.003. No difference in crude OS was observed between BRCAm+ vs BRCAm- (HR 1.19, 95% CI 0.66-2.04, p = 0.553) and BRCA1 vs BRCA2 (HR 0.56, 95% CI 0.17-1.68, p = 0.303). However, a trend for decreased OS was observed in metastatic BRCAm+ (n = 7) vs BRCAm- (n = 26) patients, (HR 2.4, 95% CI 0.72-7.16, p = 0.145). Conclusions: BRCA testing increased over time and was conducted in 26% of BC patients by the end of the study period, with most tested after BC diagnosis. BRCAm were detected in ~3% of the BC population and in 17% of tested patients. TNBC was more common in BRCAm+, correlated with BRCA1 mutations. The preliminary finding that OS does not differ according to BRCAm+/- or BRCA1/2 warrants further investigation.