# HRD-positive (genomic instability score)

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

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: HRD; HRD-positive; HRD positive; homologous recombination deficiency; genomic instability score; GIS; GIS >= 42; myChoice HRD; HRD score; genomic scar
- Tags: biomarker; brca; genome-wide

## Notes

- Triple-negative breast cancer: the HRD score threshold of 42 was set in three neoadjuvant TNBC platinum trials, where HR deficiency (score 42 or more or BRCA1/2 mutation) predicted RCB 0/I and pCR (Telli 2016); HR deficiency was present in 70.5% of 193 GeparSixto TNBCs and predicted pCR but not carboplatin benefit (Loibl 2018); HRDetect-high was 58.6% of 237 population-based genomes and prognostic on chemotherapy (Staaf 2019). In advanced disease the Myriad HRD score did not predict carboplatin benefit in TNT (Tutt 2018). No breast label uses an HRD score; the ovarian thresholds do not transfer.
- Pancreatic ductal adenocarcinoma: no genomic instability score has a pancreatic threshold or label. Homologous recombination deficiency is defined in the literature by core or biallelic gene mutation, by the unstable structural subtype or by signature 3: 19% of 262 advanced patients by gene mutation (Park 2020), and 45% of signature-defined double-strand break repair cases had no BRCA1, BRCA2 or PALB2 event at all (Connor 2017). First-line platinum benefit tracks the deficiency (hazard ratio 0.44) while non-platinum does not (Park 2020); 4 of 5 platinum-treated patients with defective DNA maintenance responded in the first whole-genome series (Waddell 2015).

## Sources

- ZEJULA prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b7f675e2-159c-490c-b6f4-3f16d9492b7d
- Lynparza prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=741ff3e3-dc1a-45a6-84e5-2481b27131aa

## Connected records

- biomarkers: [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/), [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/), [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/), [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: [Bevacizumab](https://onco.cc/drugs/bevacizumab/), [myChoice CDx](https://onco.cc/drugs/mychoice-cdx/), [Niraparib](https://onco.cc/drugs/niraparib/), [Olaparib](https://onco.cc/drugs/olaparib/)
- terms: [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/), [Platinum-sensitive / platinum-resistant](https://onco.cc/terms/platinum-sensitivity/)
- key papers: [Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-connor-mutational-signatures-immune-pancreatic-jama-oncol-2017/), [Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial](https://onco.cc/key-papers/paper-tutt-nat-med/), [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/), [Homologous recombination deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer](https://onco.cc/key-papers/paper-telli-hrd-score-platinum-tnbc-ccr-2016/), [HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures](https://onco.cc/key-papers/paper-davies-nat-med/), [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/), [Whole genomes redefine the mutational landscape of pancreatic cancer](https://onco.cc/key-papers/paper-waddell-whole-genomes-pancreatic-nature-2015/), [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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