BRCAmutated

BRCAmutated refers to tumors or cells that harbor pathogenic variants in the BRCA1 or BRCA2 genes. These genes encode proteins essential for homologous recombination, a high-fidelity repair process for double-strand DNA breaks. Loss of BRCA function leads to homologous recombination deficiency and genomic instability, which can contribute to cancer development but also creates a therapeutic vulnerability.

BRCA mutations can be germline (inherited and present in every cell) or somatic (restricted to tumor tissue). Germline BRCA1/2 mutations markedly increase lifetime risk for breast, ovarian, and other cancers, and they inform genetic counseling and family risk. Somatic BRCA mutations may occur in tumors without inherited risk and can still influence treatment decisions, particularly regarding targeted therapies.

Clinical implications of BRCAmutation include a higher likelihood of response to platinum-based chemotherapy and pronounced sensitivity to PARP inhibitors, such as olaparib, niraparib, rucaparib, and talazoparib. These inhibitors exploit the concept of synthetic lethality in BRCA-deficient cells. BRCA mutation status is commonly used to guide therapy in ovarian cancer and is increasingly applied in breast, pancreatic, and prostate cancers. It is important to note that not all BRCA variants are pathogenic; many variants are of uncertain significance and require careful interpretation.

Diagnosis and testing may be germline, somatic, or both. Germline testing uses blood or saliva samples, while somatic testing uses tumor tissue or circulating tumor DNA. Results are categorized by pathogenicity and guide treatment decisions, surveillance, and familial risk assessment.