Breast cancer risk associated with BRCA1 and BRCA2 pathogenic variants in the Eastern Chinese population

Population-based penetrance studies of breast cancer gene 1/2 (BRCA1/2) pathogenic or likely pathogenic (P/LP) variants in the Eastern Chinese population are currently lacking; thus, we aimed to investigate the penetrance of breast cancer and other malignant tumors among BRCA1/2 P/LP variant carriers using a population-based breast cancer cohort from communities in Eastern China.

Between July 2019 and March 2021, we tested 2216 breast cancer probands from Chinese communities for BRCA1/2 mutations and collected detailed information on the age, survival status, and malignancy history of first-degree relatives. The kin-cohort method was used to calculate the penetrance of breast cancer and other malignant tumors.

Of the 2216 breast cancer probands, 109 (4.90%) carried BRCA1/2 P/LP variants, 49 in the BRCA1 gene and 60 in the BRCA2 gene. The penetrance of female breast cancer by 85 years of age was 22.50% and 18.20% in BRCA1 and BRCA2 P/LP variant carriers, respectively. The penetrance of ovarian cancer by 85 years of age was 26.00% in BRCA1 P/LP variant carriers. The penetrance of other malignancies did not reach statistical significance owing to the small number of events.

Our findings showed that breast cancer penetrance among BRCA1 and BRCA2 P/LP variant carriers was 22.50% and 18.20%, respectively, which suggests that prophylactic mastectomy may not be necessary for such Chinese individuals.

ClinicalTrials.gov; https://clinicaltrials.gov/ct2/show/NCT04265937.