germline BRCA1 or BRCA2 mutation

gBRCA1/2 = germline BRCA1 or BRCA2 mutation

Breakdown:

• BRCA1 and BRCA2 are tumor suppressor genes involved in homologous recombination DNA repair.
• Mutations in these genes impair DNA repair, leading to increased risk of breast, ovarian, pancreatic, and prostate cancers.
• gBRCA = germline mutation, meaning the mutation is inherited and present in every cell of the body.
• This is distinct from sBRCA (somatic BRCA mutation), which occurs only in tumor tissue (acquired, not inherited).

Clinical relevance in breast cancer:

• In metastatic HER2– breast cancer with gBRCA1/2 mutation, NCCN and ASCO guidelines recommend:

  • PARP inhibitors (olaparib, talazoparib) as targeted therapy options, usually after progression on endocrine-based therapy or chemotherapy.
• Testing for gBRCA1/2 mutations is standard in HR+/HER2– and triple-negative metastatic breast cancer.