HRD-positive (genomic instability score)
HRD-positive means the tumour's genome carries the scars of failed double-strand break repair (or a BRCA mutation), measured as a genomic instability score. In ovarian cancer it selects niraparib, and olaparib with bevacizumab, as first-line maintenance.
Overview
The Myriad myChoice CDx combines tumour BRCA1/2 status with a genomic instability score built from loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions; the assay calls HRD-positive at a GIS of 42 or more (the PRIMA and PAOLA-1 trials' cut-off) or any deleterious BRCA mutation. Niraparib's US label defines HRD-positive status as 'a deleterious or suspected deleterious BRCA mutation, and/or genomic instability' and the olaparib plus bevacizumab first-line maintenance indication is for HRD-positive advanced ovarian cancer. Because the scar accumulates over time, HRD status is read on tumour tissue and does not capture reversion, which is why HRD-positive tumours can still be PARP-resistant.
- 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.
HRD-positive on a myChoice report (a BRCA mutation or a genomic instability score of 42 or more) means your ovarian cancer is likely to respond to PARP inhibitors: niraparib alone, or olaparib with bevacizumab, are on label as maintenance after first chemotherapy. An HRD-negative result does not rule out niraparib, whose first-line label covers all comers, but the expected benefit is smaller.
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.
HRD-positive: a deleterious or suspected deleterious tumour BRCA1/2 mutation, or a genomic instability score at or above the assay's cut-off (42 on the myChoice CDx), computed from loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions.
“Deleterious or suspected deleterious germline or somatic mutations in BRCA1 and BRCA2 genes and/or positive Genomic Instability Score”
FDA: List of FDA-Authorized Companion Diagnostic Devices| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| HRD-positive (BRCA mutation and/or genomic instability) | Niraparib | Ovarian cancer | FDA | label |
| HRD-positive | Olaparib | Ovarian cancer | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| Myriad myChoice CDx | Myriad Genetic Laboratories | Ovarian Cancer - Tissue | Olaparib | P190014/S003 (05/08/2020) |
| Myriad myChoice CDx | Myriad Genetic Laboratories | Ovarian Cancer - Tissue | Niraparib | P190014/S011 (03/10/2026) |
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.
- NCT03742895 · 2026Efficacy and Safety of Olaparib (MK-7339) in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer (MK-7339-002 / LYNK-002)
- NCT02477644 · 2019PAOLA-1 / ENGOT-ov25
- NCT02655016 · 2019PRIMA / ENGOT-OV26
- NCT07318558A Clinical Trial of Sac-TMT in People With Non-HRD Positive Advanced Ovarian Cancer (MK-2870-021)
Similar pages
not linked directly; found by shared links- TermBRCA reversion mutations
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Shares the tags biomarker, genome-wide.
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Shares myChoice CDx, Homologous recombination deficiency (HRD), High-grade serous ovarian cancer, Niraparib.
- TechnologyHRD genomic scar scores (GIS, LOH, HRDetect)
Shares myChoice CDx, Homologous recombination deficiency (HRD), High-grade serous ovarian cancer, Niraparib.
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Shares Germline BRCA1/2 pathogenic variant (gBRCAm), Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations, Homologous recombination deficiency (HRD), High-grade serous ovarian cancer.
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Shares Homologous recombination deficiency (HRD), Olaparib, Bevacizumab, Ovarian cancer.