BRCA Gene — Breast and Ovarian Cancer Genes

BRCA1 and BRCA2 are tumour suppressor genes responsible for maintaining genomic stability. They produce specialised proteins that repair double-strand breaks in deoxyribonucleic acid (DNA) through a high-fidelity mechanism known as homologous recombination repair (HRR). When functioning correctly, these proteins safeguard genetic integrity and prevent cellular mutations from accumulating.

Pathogenic variants or mutations in these genes compromise DNA repair capacity, forcing cells to rely on alternative, error-prone repair pathways. This deficiency leads to chromosomal instability and an elevated propensity for malignant transformation. BRCA mutations can be germline, meaning they are inherited from either parent and present in every cell of the body, or somatic, meaning they arise spontaneously within tumour tissue alone.

Knowing your BRCA status has profound consequences for both cancer prevention and treatment. For individuals without cancer, carrying a pathogenic variant informs personalised risk-reduction strategies, including enhanced surveillance with regular MRI scans, preventive medications, or prophylactic surgeries such as risk-reducing mastectomy or salpingo-oophorectomy. For people diagnosed with cancer, BRCA status dictates therapy choice, notably opening access to targeted PARP inhibitors and platinum-based chemotherapies that exploit the tumour's defective DNA repair mechanisms.

BRCA testing is performed using a simple blood or saliva sample to identify germline (inherited) mutations. In diagnosed cancer patients, tumour tissue testing (somatic testing) is frequently conducted alongside germline analysis to detect non-inherited alterations. Next-generation sequencing panels evaluate BRCA1 and BRCA2 alongside other high-risk cancer susceptibility genes. Pre- and post-test genetic counselling is recommended to discuss medical and familial implications.

BRCA mutations are most strongly linked to breast cancer and epithelial ovarian cancer (including fallopian tube and primary peritoneal cancers). They also confer elevated risks for prostate cancer, particularly aggressive variants, as well as pancreatic adenocarcinoma. Less commonly, BRCA2 mutations have been associated with increased lifetime risks of melanoma and male breast cancer.

Cancers harbouring BRCA mutations are exquisitely sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors, such as olaparib, niraparib, and rucaparib. These drugs induce synthetic lethality, causing irreparable DNA damage exclusively in cancer cells lacking homologous recombination repair. BRCA-mutated tumours also demonstrate superior sensitivity to platinum-based chemotherapies like carboplatin and cisplatin. Surgical planning may also incorporate bilateral mastectomy rather than breast-conserving surgery.