# Germline BRCA1/2 pathogenic variant (gBRCAm)

Source: https://onco.cc/biomarkers/brca-germline/  
OnCo record `brca-germline` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A germline BRCA1 or BRCA2 variant is inherited and present in every cell, found by a blood test. It selects PARP inhibitors in breast, ovarian, pancreatic and prostate cancer and tells relatives they may carry it too.

## Summary

Germline testing sequences BRCA1 and BRCA2 from blood or saliva and classifies variants as pathogenic, likely pathogenic, uncertain, likely benign or benign; labels use 'deleterious or suspected deleterious'. Olaparib is labelled for gBRCAm HER2-negative high-risk early breast cancer (adjuvant, OlympiA), gBRCAm HER2-negative metastatic breast cancer, first-line maintenance of gBRCAm metastatic pancreatic cancer, and germline or somatic BRCA-mutated ovarian cancer; talazoparib for gBRCAm HER2-negative advanced breast cancer; niraparib for recurrent gBRCAm ovarian cancer maintenance. BRACAnalysis CDx (Myriad) is the blood companion diagnostic on the FDA list for olaparib, talazoparib and rucaparib. A germline result triggers cascade testing of relatives and risk-reducing surgery discussions.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: gBRCA; gBRCAm; germline BRCA; germline BRCA1; germline BRCA2; BRCA carrier; inherited BRCA mutation; deleterious germline BRCA mutation
- Tags: biomarker; brca

## Notes

- Triple-negative breast cancer: germline BRCA1/2 in 11.2% of 1,824 unselected patients (BRCA1 8.5%, BRCA2 2.7%; Couch 2015), 15.4% of 207 registry patients (Sharma 2014) and 17.2% in GeparSixto (Hahnen 2017), so guidelines test every TNBC diagnosis: ASCO-SSO for all breast cancer at 65 or under and any PARP inhibitor candidate (Bedrosian 2024); in England through the National Genomic Test Directory R208 (mainstream breast testing) and R444.1 (PARP inhibitor eligibility) criteria (Conroy 2026). The result selects adjuvant olaparib after residual disease (OlympiA), olaparib or talazoparib in metastatic disease, and carboplatin, which doubled the response rate in carriers in TNT (Tutt 2018).
- Pancreatic ductal adenocarcinoma: germline BRCA2 in 1.4 to 2% and BRCA1 in 0.4 to 1% of patients, with any susceptibility gene in 4 to 10% and no family history in most carriers, which is why every diagnosis is offered germline testing (Hu 2018, Shindo 2017, Lowery 2018). The POLO threshold is a deleterious or suspected deleterious germline BRCA1 or BRCA2 variant plus no progression after at least 16 weeks of first-line platinum: maintenance olaparib gave progression-free survival 7.4 against 3.8 months (hazard ratio 0.53) with no significant overall survival difference (19.0 versus 19.2 months) but 3-year survival 33.9% against 17.8% (Golan 2019, Kindler 2022). The same result also selects platinum chemotherapy (Golan 2014).
- Prostate cancer: germline BRCA2 in 37 of 692 men with metastatic disease, 5.3%, and BRCA1 in 6, 0.9%, with no difference by family history of prostate cancer or age at diagnosis, which is why testing is offered to every man with metastatic disease rather than to those with a suggestive family history (Pritchard 2016).
- Carrying a germline BRCA mutation changes the disease and not only the options: cause-specific survival 15.7 years in non-carriers against 8.6 years in carriers, hazard ratio 1.8, with five-year metastasis-free survival in localised disease 93% against 77% (Castro 2013).
- Only 30.7% of positive germline results in a 3,607-man referral cohort were in BRCA1 or BRCA2, so a BRCA-only panel misses most of the inherited findings in this disease (Nicolosi 2019).

## Sources

- Lynparza prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa
- Talzenna prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=13839d4f-6acf-4ffb-a128-79df59319273

## Connected records

- biomarkers: [Homologous recombination repair gene mutation in prostate cancer](https://onco.cc/biomarkers/hrr-gene-mutation/), [HRD-positive (genomic instability score)](https://onco.cc/biomarkers/hrd-positive/), [Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations](https://onco.cc/biomarkers/brca-somatic/)
- cancers: [BRCA or PALB2-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/brca-palb2-pdac/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Early triple-negative breast cancer](https://onco.cc/cancers/tnbc-early/), [High-grade serous ovarian cancer](https://onco.cc/cancers/high-grade-serous-ovarian-cancer/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Metastatic triple-negative breast cancer](https://onco.cc/cancers/tnbc-metastatic/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- drugs: [BRACAnalysis CDx](https://onco.cc/drugs/bracanalysis-cdx/), [Niraparib](https://onco.cc/drugs/niraparib/), [Olaparib](https://onco.cc/drugs/olaparib/), [Rucaparib](https://onco.cc/drugs/rucaparib/), [Talazoparib](https://onco.cc/drugs/talazoparib/)
- terms: [Germline BRCA mutation (gBRCA)](https://onco.cc/terms/gbrca-mutation/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/)
- key papers: [Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer](https://onco.cc/key-papers/paper-hu-germline-mutations-pancreatic-cancer-risk-jama-2018/), [Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial](https://onco.cc/key-papers/paper-tutt-nat-med/), [Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma](https://onco.cc/key-papers/paper-shindo-germline-sporadic-pancreatic-jco-2017/), [Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection](https://onco.cc/key-papers/paper-park-hrd-pancreatic-platinum-ccr-2020/), [Germline BRCA mutation evaluation in a prospective triple-negative breast cancer registry: implications for hereditary breast and/or ovarian cancer syndrome testing](https://onco.cc/key-papers/paper-sharma-tnbc-registry-germline-brca-bcrt-2014/), [Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer](https://onco.cc/key-papers/paper-castro-germline-brca-prostate-outcomes-jco-2013/), [Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer](https://onco.cc/key-papers/paper-yurgelun-germline-second-hits-resected-pancreatic-genet-med-2019/), [Germline mutation status, pathological complete response, and disease-free survival in triple-negative breast cancer: secondary analysis of the GeparSixto randomized clinical trial](https://onco.cc/key-papers/paper-hahnen-geparsixto-germline-brca-jama-oncol-2017/), [Germline testing in patients with breast cancer: ASCO-Society of Surgical Oncology guideline](https://onco.cc/key-papers/paper-bedrosian-asco-sso-germline-testing-breast-jco-2024/), [Implementation and audit of mainstream genetic testing within a high-volume UK breast unit for pathogenic variations associated with breast cancer using the R208 and R444.1 National Test Directory criterion](https://onco.cc/key-papers/paper-conroy-nhs-r208-mainstream-testing-audit-breast-j-2026/), [Inherited DNA-repair gene mutations in men with metastatic prostate cancer](https://onco.cc/key-papers/paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016/), [Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer](https://onco.cc/key-papers/paper-couch-tnbc-germline-17-genes-jco-2015/), [Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer](https://onco.cc/key-papers/paper-isaacsson-velho-intraductal-germline-dna-repair-prostate-2018/), [Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers](https://onco.cc/key-papers/paper-golan-brca-pancreatic-platinum-survival-bjc-2014/), [Phase II study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic variant in BRCA1, BRCA2, or PALB2](https://onco.cc/key-papers/paper-reiss-rucaparib-maintenance-brca-palb2-pancreatic-jco-2021/), [POLO final overall survival: maintenance olaparib versus placebo in germline BRCA-mutated metastatic pancreatic cancer](https://onco.cc/key-papers/paper-polo-overall-survival-olaparib-gbrca-pancreatic-jco-2022/), [POLO: maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer](https://onco.cc/key-papers/paper-polo-olaparib-maintenance-gbrca-pancreatic-nejm-2019/), [Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines](https://onco.cc/key-papers/paper-nicolosi-germline-variants-prostate-testing-guidelines-jama-oncol-2019/), [Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms](https://onco.cc/key-papers/paper-lowery-prospective-germline-exocrine-pancreatic-jnci-2018/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/)

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