Germline and Tumor BRCA1/2 Pathogenic Variants in Chinese Triple-negative Breast Carcinomas

Abstract PurposeThe cost-effectiveness of BRCA1/2 screening for all newly diagnosed breast cancer remains controversial with respect to standard treatment. Further evidences that include incidence and outcome of BRCA1/2 pathogenic variants (PV) screened based on age or family history (FH) are needed to fully justify this conclusion. We aimed to investigate germline and tumor BRCA1/2 PV based on age screening in Chinese triple-negative breast cancer (TNBC) patients. MethodsPaired blood and tumor DNA from 124 unselected Chinese TNBC patients with less than or equal to 55 years were collected and analyzed for BRCA1/2 PV. Clinicopathological characteristics including age at diagnosis, FH and follow-up data were collected for further analysis. ResultsThe entire frequency of germline and tumor BRCA1/2 PV was 21.0% and 25%, respectively. Among them, 20 (16.1%) germline and 5 (4.0%) somatic BRCA1/2 single-nucleotide variant/insertion/deletions were found by NGS testing, 6 (4.8%) BRCA1 large genomic rearrangements were detected in blood DNA by MPLA. There was significant correlation between FH and germline BRCA1/2 PV among these patients. Patients with tumor BRCA1/2 mutations had significant improvements than non-carriers in PFS ( p =0.047). No significant impacts were found between various mutation status in OS outcomes. No significant differences were found between BRCA1 or BRCA2 and non-carriers in PFS or OS. ConclusionThere is a high incidence of germline and tumor BRCA1/2 PVs in Chinese TNBC patients with less than or equal to 55 years old. Tumor BRCA1/2 PV carriers showed an improved survival outcome. Our results suggest that BRCA1/2 PVs testing addressed within each specific clinical scenario could be more cost-effective for patients.