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Germline BRCA mutation (gBRCA)

aka gBRCA, gBRCAm, BRCA-mutated, BRCA-mutant, BRCA mutation, BRCA carriers, BRCA carrier, BRCA1/2, BRCA1, BRCA2, sBRCA, somatic BRCA, BRCA-deficient, BRCA wild-type, BRCA status, HRR mutation, HRR-mutant, HRRm, PALB2

An inherited fault in the BRCA1 or BRCA2 gene, present in every cell from birth, that greatly raises the risk of breast, ovarian, prostate and pancreatic cancer and makes those cancers sensitive to PARP inhibitors and platinum.

About 1 in 300-400 people (1 in 40 in Ashkenazi Jews) carries a pathogenic germline BRCA variant; lifetime breast cancer risk is 60-70% and ovarian 20-45%. Testing is now offered to all ovarian, pancreatic and metastatic prostate cancer patients, to triple-negative and young breast cancer patients, and increasingly to all breast cancer patients, with cascade testing of relatives. Carriers get intensified screening, risk-reducing mastectomy and salpingo-oophorectomy, and PARP inhibitors: adjuvant olaparib (OlympiA), maintenance in ovarian cancer (SOLO-1) and in prostate and pancreatic cancer. Somatic (tumour-only) BRCA mutations respond similarly; HRR genes such as PALB2, ATM and RAD51C extend the concept.

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Pathology & biomarkers

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