{"entity":{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","aka":[],"tldr":"A tumour that cannot properly repair double-strand DNA breaks, usually because of BRCA or related gene loss.","summary":"Homologous recombination deficiency (HRD) describes a tumour that cannot properly repair double-strand DNA breaks, usually because BRCA1, BRCA2 or a related gene has been lost. It is detected by a BRCA1/2 mutation or by genomic-scar scores such as the myChoice CDx GIS at a threshold of 42 or FoundationOne LOH, and it predicts benefit from PARP inhibitors and platinum. HRD is common in high-grade serous ovarian cancer and present in a substantial minority of Triple-negative breast cancer (TNBC). The term sits with the HRD & BRCA testing technology and the BRCA1 / BRCA2 (HRD) and PARP targets, and it is used by the PRIMA and PAOLA-1 trials, Rucaparib, the pairing of PARP inhibitor plus bevacizumab maintenance, Sabine Linn and the bottleneck on biomarker validation.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Homologous_recombination","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Homologous_recombination"}],"tags":[],"related":["genome-wide-loss-of-heterozygosity"],"cancers":["prostate","prostate-mcrpc"],"sections":[],"technologies":["hrd-testing"],"targets":["brca","parp"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["genome-wide-loss-of-heterozygosity"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015"],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},"route":"/terms/hrd/","neighbours":{"term":[{"id":"brca-reversion-mutations","kind":"term","name":"BRCA reversion mutations","route":"/terms/brca-reversion-mutations/"},{"id":"genome-instability-mutation","kind":"term","name":"Enabling characteristic: genome instability and mutation","route":"/terms/genome-instability-mutation/"},{"id":"gene-amplification","kind":"term","name":"Gene amplification and copy-number change","route":"/terms/gene-amplification/"},{"id":"genome-wide-loss-of-heterozygosity","kind":"term","name":"Genome-wide loss of heterozygosity (gLOH)","route":"/terms/genome-wide-loss-of-heterozygosity/"},{"id":"gbrca-mutation","kind":"term","name":"Germline BRCA mutation (gBRCA)","route":"/terms/gbrca-mutation/"},{"id":"hgsoc","kind":"term","name":"High-grade serous ovarian carcinoma (HGSOC)","route":"/terms/hgsoc/"},{"id":"hrd-in-breast-cancer","kind":"term","name":"Homologous recombination deficiency (HRD) in breast cancer","route":"/terms/hrd-in-breast-cancer/"},{"id":"platinum-sensitivity","kind":"term","name":"Platinum-sensitive / platinum-resistant","route":"/terms/platinum-sensitivity/"},{"id":"prostate-crpc-sequencing","kind":"term","name":"What follows what in castration-resistant prostate cancer","route":"/terms/prostate-crpc-sequencing/"},{"id":"prostate-hrr-eligibility","kind":"term","name":"Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters","route":"/terms/prostate-hrr-eligibility/"}],"cancer":[{"id":"brca-palb2-pdac","kind":"cancer","name":"BRCA or PALB2-mutant pancreatic ductal adenocarcinoma","route":"/cancers/brca-palb2-pdac/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"id":"high-grade-serous-ovarian-cancer","kind":"cancer","name":"High-grade serous ovarian cancer","route":"/cancers/high-grade-serous-ovarian-cancer/"},{"id":"prostate-mcrpc","kind":"cancer","name":"Metastatic castration-resistant prostate cancer","route":"/cancers/prostate-mcrpc/"},{"id":"pancreatic-acinar-cell-carcinoma","kind":"cancer","name":"Pancreatic acinar cell carcinoma","route":"/cancers/pancreatic-acinar-cell-carcinoma/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"platinum-sensitive-ovarian-cancer","kind":"cancer","name":"Platinum-sensitive ovarian cancer","route":"/cancers/platinum-sensitive-ovarian-cancer/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"hrd-testing","kind":"technology","name":"HRD & BRCA testing","route":"/technologies/hrd-testing/"},{"id":"hrd-genomic-scar-scores","kind":"technology","name":"HRD genomic scar scores (GIS, LOH, HRDetect)","route":"/technologies/hrd-genomic-scar-scores/"},{"id":"rad51-foci-assay","kind":"technology","name":"RAD51 foci assay (functional HRD test)","route":"/technologies/rad51-foci-assay/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"target":[{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"parp","kind":"target","name":"PARP","route":"/targets/parp/"}],"paper":[{"id":"paper-quigley-brca2-reversion-cfdna-parp-resistance-cancer-discov-2017","kind":"paper","name":"Analysis of circulating cell-free DNA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors","route":"/key-papers/paper-quigley-brca2-reversion-cfdna-parp-resistance-cancer-discov-2017/"},{"id":"paper-asco-biomarkers-metastatic-breast-cancer-guideline-jco-2022","kind":"paper","name":"Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update","route":"/key-papers/paper-asco-biomarkers-metastatic-breast-cancer-guideline-jco-2022/"},{"id":"paper-tutt-nat-med","kind":"paper","name":"Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial","route":"/key-papers/paper-tutt-nat-med/"},{"id":"paper-wardell-biliary-drivers-germline-j-hepatol-2018","kind":"paper","name":"Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations","route":"/key-papers/paper-wardell-biliary-drivers-germline-j-hepatol-2018/"},{"id":"paper-park-hrd-pancreatic-platinum-ccr-2020","kind":"paper","name":"Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection","route":"/key-papers/paper-park-hrd-pancreatic-platinum-ccr-2020/"},{"id":"paper-castro-germline-brca-prostate-outcomes-jco-2013","kind":"paper","name":"Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer","route":"/key-papers/paper-castro-germline-brca-prostate-outcomes-jco-2013/"},{"id":"paper-taylor-germline-brca2-evolutionary-trajectories-nat-commun-2017","kind":"paper","name":"Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories","route":"/key-papers/paper-taylor-germline-brca2-evolutionary-trajectories-nat-commun-2017/"},{"id":"paper-telli-hrd-score-platinum-tnbc-ccr-2016","kind":"paper","name":"Homologous recombination deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer","route":"/key-papers/paper-telli-hrd-score-platinum-tnbc-ccr-2016/"},{"id":"paper-davies-nat-med","kind":"paper","name":"HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures","route":"/key-papers/paper-davies-nat-med/"},{"id":"paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016","kind":"paper","name":"Inherited DNA-repair gene mutations in men with metastatic prostate cancer","route":"/key-papers/paper-pritchard-inherited-dna-repair-metastatic-prostate-nejm-2016/"},{"id":"paper-isaacsson-velho-intraductal-germline-dna-repair-prostate-2018","kind":"paper","name":"Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer","route":"/key-papers/paper-isaacsson-velho-intraductal-germline-dna-repair-prostate-2018/"},{"id":"paper-weinberg-biliary-profiling-jgo-2019","kind":"paper","name":"Molecular profiling of biliary cancers reveals distinct molecular alterations and potential therapeutic targets","route":"/key-papers/paper-weinberg-biliary-profiling-jgo-2019/"},{"id":"paper-paola-1-nejm-2019","kind":"paper","name":"PAOLA-1: olaparib added to bevacizumab maintenance in newly diagnosed ovarian cancer, with benefit confined to HRD-positive tumours","route":"/key-papers/paper-paola-1-nejm-2019/"},{"id":"paper-profound-nejm-2020","kind":"paper","name":"PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations","route":"/key-papers/paper-profound-nejm-2020/"},{"id":"paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019","kind":"paper","name":"Prospective comprehensive genomic profiling of 3,476 primary and metastatic prostate tumours","route":"/key-papers/paper-chung-comprehensive-genomic-profiling-prostate-jco-po-2019/"},{"id":"paper-aguirre-real-time-genomic-characterisation-pancreatic-cancer-discov-2018","kind":"paper","name":"Real-time genomic characterization of advanced pancreatic cancer to enable precision medicine","route":"/key-papers/paper-aguirre-real-time-genomic-characterisation-pancreatic-cancer-discov-2018/"},{"id":"paper-solo-1-nejm-2018","kind":"paper","name":"SOLO-1: two years of olaparib maintenance after first-line chemotherapy for BRCA-mutated ovarian cancer","route":"/key-papers/paper-solo-1-nejm-2018/"},{"id":"paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","kind":"paper","name":"SU2C-PCF: integrative clinical genomics of advanced prostate cancer","route":"/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/"},{"id":"paper-loibl-geparsixto-survival-hrd-ann-oncol-2018","kind":"paper","name":"Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto","route":"/key-papers/paper-loibl-geparsixto-survival-hrd-ann-oncol-2018/"},{"id":"paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","kind":"paper","name":"TCGA: the molecular taxonomy of primary prostate cancer","route":"/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/"},{"id":"paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015","kind":"paper","name":"TOPARP-A: DNA-repair defects and olaparib in metastatic prostate cancer","route":"/key-papers/paper-mateo-toparp-a-olaparib-dna-repair-nejm-2015/"},{"id":"paper-abida-triton2-rucaparib-brca-jco-2020","kind":"paper","name":"TRITON2: rucaparib in men with metastatic castration-resistant prostate cancer harbouring a BRCA1 or BRCA2 alteration","route":"/key-papers/paper-abida-triton2-rucaparib-brca-jco-2020/"},{"id":"paper-fizazi-triton3-rucaparib-nejm-2023","kind":"paper","name":"TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer","route":"/key-papers/paper-fizazi-triton3-rucaparib-nejm-2023/"},{"id":"paper-waddell-whole-genomes-pancreatic-nature-2015","kind":"paper","name":"Whole genomes redefine the mutational landscape of pancreatic cancer","route":"/key-papers/paper-waddell-whole-genomes-pancreatic-nature-2015/"},{"id":"paper-staaf-tnbc-whole-genome-scan-b-nat-med-2019","kind":"paper","name":"Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study","route":"/key-papers/paper-staaf-tnbc-whole-genome-scan-b-nat-med-2019/"}],"trial":[{"id":"paola-1","kind":"trial","name":"PAOLA-1 / ENGOT-ov25","route":"/trials/paola-1/"},{"id":"prima","kind":"trial","name":"PRIMA / ENGOT-OV26","route":"/trials/prima/"},{"id":"tnt","kind":"trial","name":"TNT (Triple Negative Trial)","route":"/trials/tnt/"},{"id":"triton3","kind":"trial","name":"TRITON3","route":"/trials/triton3/"}],"drug":[{"id":"mychoice-cdx","kind":"drug","name":"myChoice CDx","route":"/drugs/mychoice-cdx/"},{"id":"rucaparib","kind":"drug","name":"Rucaparib","route":"/drugs/rucaparib/"}],"pairing":[{"id":"parp-plus-bevacizumab","kind":"pairing","name":"PARP inhibitor + bevacizumab maintenance (HRD-positive)","route":"/pairings/parp-plus-bevacizumab/"}],"roadmap":[{"id":"tnbc-roadmap","kind":"roadmap","name":"Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem","route":"/roadmaps/tnbc-roadmap/"}],"biomarker":[{"id":"brca-germline","kind":"biomarker","name":"Germline BRCA1/2 pathogenic variant (gBRCAm)","route":"/biomarkers/brca-germline/"},{"id":"hrr-gene-mutation","kind":"biomarker","name":"Homologous recombination repair gene mutation in prostate cancer","route":"/biomarkers/hrr-gene-mutation/"},{"id":"hrd-positive","kind":"biomarker","name":"HRD-positive (genomic instability score)","route":"/biomarkers/hrd-positive/"},{"id":"brca-somatic","kind":"biomarker","name":"Tumour (somatic or germline) BRCA1/2 mutation and HRR gene alterations","route":"/biomarkers/brca-somatic/"}],"person":[{"id":"sabine-linn","kind":"person","name":"Sabine Linn","route":"/people/sabine-linn/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-hereditary-risk","kind":"bottleneck","name":"Inherited risk is mostly unidentified","route":"/bottlenecks/b-hereditary-risk/"}],"idea":[{"id":"idea-tr2-hrd-functional-standard","kind":"idea","name":"A functional test for homologous recombination deficiency validated across laboratories","route":"/ideas/idea-tr2-hrd-functional-standard/"},{"id":"idea-tr2-marker-stratified-default","kind":"idea","name":"Test the drug in biomarker-negative patients too, so the biomarker can be validated","route":"/ideas/idea-tr2-marker-stratified-default/"}],"collection":[{"id":"ovarian-cancer-research-alliance","kind":"collection","name":"Ovarian Cancer Research Alliance (OCRA)","route":"/collections/ovarian-cancer-research-alliance/"}],"pathway":[{"id":"base-excision-repair-parp","kind":"pathway","name":"Base excision repair, PARP & alkylation damage","route":"/pathways/base-excision-repair-parp/"},{"id":"homologous-recombination-repair","kind":"pathway","name":"Double-strand break repair: HR versus end joining","route":"/pathways/homologous-recombination-repair/"},{"id":"mutagenesis-signatures","kind":"pathway","name":"Mutagenesis & mutational signatures","route":"/pathways/mutagenesis-signatures/"},{"id":"synthetic-lethality-map","kind":"pathway","name":"Synthetic lethality: paired dependencies","route":"/pathways/synthetic-lethality-map/"}],"company":[{"id":"arcagy-gineco","kind":"company","name":"ARCAGY-GINECO","route":"/companies/arcagy-gineco/"}]}}