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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.
In plain words · DNA repair genes. Inheriting a broken copy raises breast and ovarian cancer risk, but tumours that lose them become uniquely vulnerable to PARP inhibitors and platinum.
Showing the target this term concerns: BRCA1 / BRCA2 (HRD).
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
This is what the NHS R208 pathway yields in practice: a one-in-seven positive rate among the eligible, at the cost of clinician time spent on eligibility scoring.
An argument for universal rather than criteria-based germline testing at diagnosis, with turnaround fast enough to inform surgery; for TNBC patients, who are already eligible, the lesson is timing.
For TNBC, which is diagnosed young and is the PARP inhibitor-eligible subtype, the guideline makes germline testing part of the diagnostic workup rather than a referral decision.
Olaparib maintenance remains a standard option because of its progression-free benefit, tolerability and long-term survivors, but patients should know that it has not been shown to extend average survival.
TROP2 IHC does not gate sacituzumab govitecan: the label requires no test, and the corpus records TROP2 as an expression readout without a threshold.
It established plasma profiling as a routine alternative to tissue for the BRCA question in advanced prostate cancer, with a sensible rule attached: if plasma finds nothing actionable, go back to tissue. It also documents at scale both the extra resistance information plasma gives and the clonal haematopoiesis noise that comes with it.
The document that made biomarker testing part of routine pancreatic cancer care in the United States; the 2018 version it built on fixed the second-line chemotherapy sequence still used in most guidelines.
Germline and tumour testing for homologous recombination repair genes is now standard in metastatic prostate cancer, and olaparib is approved for BRCA-mutated disease after a hormonal agent.
Shares Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer, Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories, Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer, Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines.
Shares Inherited breast cancer in Nigerian women, The impact of expanded access to germline high penetrance genetic testing for women with a new diagnosis of invasive breast cancer or high-grade DCIS, Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing, Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms.
Shares Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer, Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer, Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines, POLO: maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer.
Shares POLO final overall survival: maintenance olaparib versus placebo in germline BRCA-mutated metastatic pancreatic cancer, Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers, Metastatic Pancreatic Cancer: ASCO Guideline Update, POLO: maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer.
Shares BRCA reversion mutations, Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms, TRITON2: rucaparib in men with metastatic castration-resistant prostate cancer harbouring a BRCA1 or BRCA2 alteration, Homologous recombination repair gene mutation in prostate cancer.
Shares Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms, Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma, Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer, Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines.
Shares Germline testing in patients with breast cancer: ASCO-Society of Surgical Oncology guideline, Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer, BRACAnalysis CDx, EMBRACA.
Shares Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial, Whole genomes redefine the mutational landscape of pancreatic cancer, Homologous recombination repair gene mutation in prostate cancer, Germline BRCA1/2 pathogenic variant (gBRCAm).