OnCo
technologiesTechnologyStandard of care

HRD & BRCA testing

Tests that reveal whether a tumour has a broken DNA repair system, which predicts response to PARP inhibitors and platinum.

Germline and somatic BRCA1/2 sequencing plus genomic-scar scores (myChoice CDx GIS, FoundationOne LOH) define HRD. Functional assays (RAD51 foci) and mutational signature 3 are emerging alternatives that may capture reversion.

Schematic · not to scale
Unrepaired double-strand break · Genomic scars (LOH, TAI, LST)

How it works

Loss of heterozygosity, telomeric allelic imbalance, and large-scale transitions summed into a genomic instability score.

Strengths
  • Extends PARP-inhibitor benefit beyond BRCA carriers
Limitations
  • Scar is permanent even after resistance emerges
  • Threshold debates

Key papers

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rctNew England Journal of Medicine 2019changed practice
PAOLA-1: olaparib added to bevacizumab maintenance in newly diagnosed ovarian cancer, with benefit confined to HRD-positive tumours

Women with newly diagnosed advanced ovarian cancer should have their tumour tested for BRCA mutations and homologous recombination deficiency, because those who are HRD-positive gain years of additional disease control and better survival from adding olaparib to bevacizumab maintenance. Those who are HRD-negative gain nothing from olaparib in this combination and should not be exposed to its toxicity and cost. HRD testing has become a routine part of ovarian cancer care as a result.

Latest papers

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Literature trend408 papers in the last 12 months+30% vs prior 12How this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

Query for this technology: (TITLE:"homologous recombination deficiency" OR ABSTRACT:"homologous recombination deficiency" OR TITLE:"HRD testing" OR ABSTRACT:"HRD testing" OR TITLE:"HRD score" OR ABSTRACT:"HRD score"). Results are unfiltered search hits about HRD & BRCA testing, not a curated reading list.

Connected

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cancers

1
Ovarian cancer

fronts

1
Diagnostics & Biomarkers

targets

2
BRCA1 / BRCA2 (HRD)PARP

institutions

2
ARCAGY-GINECOSociety of Gynecologic Oncology

pathways

4
DNA damage response & homologous recombinationDouble-strand break repair: HR versus end joiningMutagenesis & mutational signaturesSynthetic lethality: paired dependencies

terms

2
Enabling characteristic: genome instability and mutationHomologous recombination deficiency (HRD)

ideas

1
A functional test for homologous recombination deficiency validated across laboratories

people

1
Mary-Claire King

bottlenecks

1
Biomarkers are not validated or standardised

key papers

1
PAOLA-1: olaparib added to bevacizumab maintenance in newly diagnosed ovarian cancer, with benefit confined to HRD-positive tumours