Pathogenic variants in the BRCA 1 and BRCA2 genes: what is important for a practicing gynecologist to know

The BRCA1 and BRCA2 genes encode amino acid sequences in the nuclear proteins that are involved in the regulation of DNA damage repair and cell division. Pathogenic variants in the BRCA1 and BRCA2 gene cause chromosomal instability and malignant transformation of cells in the breast, ovaries, and other organs. The lifetime cumulative risk for breast cancer (BC) is as much as 72% and the risk for ovarian cancer (OC) is as much as 64% for female carriers of a pathogenic variant in the BRCA1. The risk for BC and OC for those of this variant in the BRCA2 gene is 69 and 17%, respectively. To a lesser extent, the carriers of pathogenic variants in the BRCA genes are at increased risk for other malignant neoplasms, such as melanoma, endometrial, pancreatic, peritoneal, and prostate and colon cancers. The presence of pathogenic variants in the BRCA1 and BRCA2 genes in a patient largely determines the choice of treatment policy, as well as preventive measures. Studies have shown that population screening for pathogenic variants in the BRCA1 and BRCA2 genes is cost-effective and can be used as an effective strategy to reduce the risk of BC/OC. Conclusion: A clear algorithm of actions should be elaborated to identify pathogenic variants in the BRCA1 and BRCA2 genes in individuals without a history of BC/OC, by taking into account the patient's age and plans for the implementation of reproductive function. There is a need for further investigations on the rehabilitation of patients after preventive surgery, including the safety of hormone replacement therapy, the adjustment of optimal doses, the design of drugs, and the determination of the duration of their use.

BRCA, BRCA, hereditary breast and ovarian cancers, preventive surgery, hormone replacement therapy