# Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations

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

## TL;DR

Tumour BRCA testing finds BRCA1/2 mutations in the cancer itself, whether inherited or acquired; wider panels add other repair genes such as ATM and PALB2. Ovarian and prostate cancer labels accept the tumour result for PARP inhibitors.

## Summary

Sequencing tumour tissue or plasma DNA detects BRCA1/2 mutations regardless of origin (about a third of ovarian tumour BRCA mutations are somatic only) and, on larger panels, alterations in the homologous recombination repair genes. Olaparib is labelled for germline or somatic BRCA-mutated ovarian cancer (first-line and recurrent maintenance), for HRR gene-mutated metastatic castration-resistant prostate cancer after enzalutamide or abiraterone (PROfound; genes listed on the FoundationOne CDx claim), and with abiraterone for BRCA-mutated mCRPC; rucaparib for BRCA-mutated ovarian cancer and mCRPC from plasma; talazoparib with enzalutamide for HRR gene-mutated mCRPC, the label listing ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2 and RAD51C. FoundationOne CDx and Liquid CDx, FoundationFocus CDxBRCA and myChoice CDx carry the tumour claims.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: somatic BRCA; sBRCA; tumor BRCA; tBRCA; BRCAm; BRCA-mutated; HRR gene mutation; HRRm; homologous recombination repair gene alteration; ATM mutation; PALB2 mutation
- Tags: biomarker; brca

## Notes

- Triple-negative breast cancer: somatic biallelic BRCA1/2 loss was found in 9 of 237 whole genomes against 20 germline (Staaf 2019) and somatic biallelic homologous recombination gene loss rose from 2% in early to 7% in metastatic TNBC (Bertucci 2019); tumour BRCA mutation was one arm of the GeparSixto HRD definition (Loibl 2018). No breast label accepts a somatic-only BRCA result for a PARP inhibitor.
- Pancreatic ductal adenocarcinoma: somatic homologous recombination gene mutations added 4 percentage points to the 15% germline rate among 262 advanced patients, and somatic and germline cases behaved alike for genomic instability and outcome, with core (BRCA1, BRCA2, PALB2) and biallelic alterations carrying the platinum benefit (Park 2020). Maintenance rucaparib produced a response in 1 of 2 somatic BRCA2 patients (Reiss 2021). A germline variant without a somatic second hit, the case in more than half of carriers, may not give a repair-deficient tumour (Yurgelun 2019). No pancreatic label accepts a somatic-only result.
- Prostate cancer: BRCA2, BRCA1 and ATM aberrations together were 19.3% of 150 metastatic castration-resistant tumours (Robinson 2015), and cBioPortal gives BRCA2 mutation in 37 of 444 samples, 8.3%, in prad_su2c_2019 with deep deletion in 13 more.
- Somatic and germline alterations behave the same way on treatment: in TRITON2, response rates to rucaparib were similar whether the BRCA alteration was germline or somatic, and similar for BRCA1 and BRCA2, with higher PSA response rates in BRCA2 (Abida 2020).
- Plasma detects them reliably when the tumour sheds enough DNA: 67 of 72 tissue-detected BRCA1 or BRCA2 mutations were also found in plasma, 93%, including 100% of predicted germline variants (Tukachinsky 2021). At PARP inhibitor resistance the gene is often repaired by a multiclonal reversion that only plasma reveals (Quigley 2017).

## Sources

- Lynparza prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa
- Rubraca prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0295d202-1cfe-7659-e063-6294a90a476e
- Talzenna prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=13839d4f-6acf-4ffb-a128-79df59319273

## Connected records

- biomarkers: [Circulating tumour DNA fraction (and what a negative plasma result means)](https://onco.cc/biomarkers/ctdna-tumour-fraction/), [Folate receptor alpha expression (FRα-positive, PS2+ >= 75%)](https://onco.cc/biomarkers/folr1-expression/), [Germline BRCA1/2 pathogenic variant (gBRCAm)](https://onco.cc/biomarkers/brca-germline/), [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/)
- cancers: [BRCA or PALB2-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/brca-palb2-pdac/), [High-grade serous ovarian cancer](https://onco.cc/cancers/high-grade-serous-ovarian-cancer/), [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Platinum-sensitive ovarian cancer](https://onco.cc/cancers/platinum-sensitive-ovarian-cancer/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- drugs: [FoundationOne CDx / Liquid CDx](https://onco.cc/drugs/foundationone-cdx/), [myChoice CDx](https://onco.cc/drugs/mychoice-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: [BRCA reversion mutations](https://onco.cc/terms/brca-reversion-mutations/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/), [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/)
- key papers: [Analysis of circulating cell-free DNA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors](https://onco.cc/key-papers/paper-quigley-brca2-reversion-cfdna-parp-resistance-cancer-discov-2017/), [Genomic analysis of circulating tumour DNA in 3,334 patients with advanced prostate cancer identifies targetable BRCA alterations and AR resistance mechanisms](https://onco.cc/key-papers/paper-tukachinsky-ctdna-3334-advanced-prostate-ccr-2021/), [Genomic characterization of metastatic breast cancers](https://onco.cc/key-papers/paper-bertucci-metastatic-breast-genomics-nature-2019/), [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 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/), [HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures](https://onco.cc/key-papers/paper-davies-nat-med/), [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/), [SU2C-PCF: integrative clinical genomics of advanced prostate cancer](https://onco.cc/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/), [Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto](https://onco.cc/key-papers/paper-loibl-geparsixto-survival-hrd-ann-oncol-2018/), [TRITON2: rucaparib in men with metastatic castration-resistant prostate cancer harbouring a BRCA1 or BRCA2 alteration](https://onco.cc/key-papers/paper-abida-triton2-rucaparib-brca-jco-2020/), [Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study](https://onco.cc/key-papers/paper-staaf-tnbc-whole-genome-scan-b-nat-med-2019/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/)

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JSON: https://onco.cc/api/v1/entities/brca-somatic.json