Loading
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.
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.
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.
A pathogenic germline BRCA result means the change is inherited. For your treatment it opens PARP inhibitor tablets (olaparib, talazoparib, niraparib or rucaparib depending on the cancer), including a year of olaparib after chemotherapy in high-risk early breast cancer. For your family it means close relatives can be tested and, if positive, offered screening or preventive surgery. A 'variant of uncertain significance' is not a positive result.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
A pathogenic or likely pathogenic (deleterious or suspected deleterious) BRCA1 or BRCA2 variant detected in germline DNA from blood by sequencing and large rearrangement analysis.
“deleterious or suspected deleterious gBRCAm human epidermal growth factor receptor 2 (HER2)-negative high risk early breast cancer”
Lynparza prescribing information| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| Deleterious or suspected deleterious gBRCAm | Olaparib | Breast cancer (all types) | FDA | label |
| Deleterious or suspected deleterious gBRCAm | Olaparib | Pancreatic ductal adenocarcinoma | FDA | label |
| Deleterious or suspected deleterious gBRCAm | Talazoparib | Breast cancer (all types) | FDA | label |
| Deleterious or suspected deleterious gBRCAmut | Niraparib | Ovarian cancer | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| BRACAnalysis CDx | Myriad Genetic Laboratories | Breast Cancer - Whole Blood | Olaparib | P140020/S012 (01/12/2018) |
| BRACAnalysis CDx | Myriad Genetic Laboratories | Breast Cancer - Whole Blood | Talazoparib | P140020/S015 (10/16/2018) |
| BRACAnalysis CDx | Myriad Genetic Laboratories | Ovarian Cancer - Whole Blood | Olaparib | P140020 (12/19/2014) |
| BRACAnalysis CDx | Myriad Genetic Laboratories | Pancreatic Cancer - Whole Blood | Olaparib | P140020/S019 (12/27/2019) |
| BRACAnalysis CDx | Myriad Genetic Laboratories | Metastatic Castrate Resistant Prostate Cancer (mCRPC) - Whole Blood | Olaparib | P140020/S020 (05/19/2020) |
Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.
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.
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.
It is the evidence that PALB2 and somatic BRCA2 belong in the PARP inhibitor conversation even though the olaparib label stops at germline BRCA.
It defines who a homologous recombination result should send to platinum: core-gene and biallelic carriers, germline or somatic, rather than any repair-gene variant.
A germline result is not the whole story: without loss of the second allele the tumour may not be repair-deficient, which is why tumour sequencing and, in trials, HRD signatures are read alongside.
Germline testing for every pancreatic cancer patient, platinum first line for BRCA carriers, and olaparib maintenance for those who respond are all downstream of POLO.
It is the second half of the argument for unselected germline testing, and it widens the target beyond BRCA: two thirds of the actionable inherited findings in prostate cancer are in other genes, including the mismatch repair genes that open a checkpoint inhibitor route.
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, POLO: maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer, BRCA or PALB2-mutant pancreatic ductal adenocarcinoma and the tag brca.
Shares Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, Homologous recombination repair gene mutation in prostate cancer, Germline vs somatic mutations, BRCA1 / BRCA2 (HRD) and the tag biomarker.
Shares HRD-positive (genomic instability score), Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, High-grade serous ovarian cancer, Ovarian cancer and the tag biomarker.
Shares Metastatic triple-negative breast cancer, Metastatic castration-resistant prostate cancer, Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer and the tag biomarker.
Shares Rucaparib, Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, Homologous recombination repair gene mutation in prostate cancer, High-grade serous ovarian cancer.
Shares Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer, 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, Prospective evaluation of germline alterations in patients with exocrine pancreatic neoplasms, Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma.
Shares Metastatic triple-negative breast cancer, Breast cancer (all types), Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer and the tag biomarker.
Shares Breast cancer (all types), Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer and the tag biomarker.