Germline variants analysis of Chinese breast cancer patients reveals numerous alterations in homologous recombination genes.

Abstract

Purpose: We aimed to identify the pathogenic variants of homologous recombination (HR) genes and analyze the correlation between the pathogenic variants and clinical characteristics in Chinese breast cancer patients.

Methods: A cohort of 178 breast cancer patients participated in this study. We assessed genomic alterations using a 23-gene panel, which includes most of the HR-related genes and DNA mismatch repair (MMR) gene, through next-generation sequencing. The pathogenicity of variants was determined based on the American College of Medical Genetics and Genomics standards and guidelines. The correlation between these pathogenic variants and the clinical characteristics of the patients was investigated.

Results: 26 pathogenic variants, including one novel suspected pathogenic variant, were detected in 28 (15.7%) patients. These variants occurred in 7 HR-related genes: BRCA1, BRCA2, PALB2, RAD51D, RAD50, BRIP1, and ATM. The frequency of BRCA1 variants was higher in the younger group (8.9%) compared to the older group (2.6%), while the trend was reversed for BRCA2 (3.0% vs. 7.8%). All three patients with the pathogenic variant (p.Lys91fs) in RAD51D were diagnosed with triple-negative breast cancer.

Conclusions: HR-gene testing in breast cancer could help to find new suspected pathogenic variants and increase the clinical benefit of multi-gene testing for breast cancer.