Germline BRCA1/2 pathogenic variant (gBRCAm)
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
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