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A tumour that cannot properly repair double-strand DNA breaks, usually because of BRCA or related gene loss.
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.
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.
Showing the target this term concerns: BRCA1 / BRCA2 (HRD).
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
The randomised proof for PARP inhibition in BRCA-altered prostate cancer, and the clearest evidence that the homologous recombination repair gene list should not be used as a single yes-or-no test. ATM-altered disease needs a different answer, and does not yet have one.
Confirms that the TROP2 antibody-drug conjugates are given without a TROP2 test and that PD-L1 remains the one selection assay in metastatic triple-negative disease, which is why assay harmonisation matters.
It defines who a homologous recombination result should send to platinum: core-gene and biallelic carriers, germline or somatic, rather than any repair-gene variant.
Germline and tumour testing for homologous recombination repair genes is now standard in metastatic prostate cancer, and olaparib is approved for BRCA-mutated disease after a hormonal agent.
The trial behind the second PARP inhibitor licensed in prostate cancer, and the evidence that a somatic BRCA alteration predicts response as well as an inherited one. Together with TOPARP-A it is why tumour as well as germline sequencing is recommended in metastatic disease.
The largest single-platform comparison; the abstract gives directions rather than percentages, so the figures on OnCo come from the other cohorts, but it supports testing gallbladder cancer for HER2, repair defects and immunotherapy markers.
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.
What a prostate cancer sequencing report looks like in practice, and the numerical basis for two clinical rules: do not expect checkpoint immunotherapy to work unless the tumour is mismatch repair deficient, and do not treat a CDK12 alteration as if it were a BRCA alteration.
Shares PRIMA / ENGOT-OV26, Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters, myChoice CDx, ARCAGY-GINECO.
Shares Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer, Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories, Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer, Real-time genomic characterization of advanced pancreatic cancer to enable precision medicine.
Shares Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer, TRITON3, Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters, PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations.
Shares Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis and poor survival outcomes in prostate cancer, Intraductal and ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer, Enabling characteristic: genome instability and mutation, Whole genomes redefine the mutational landscape of pancreatic cancer.
Shares PARP inhibitor + bevacizumab maintenance (HRD-positive), A functional test for homologous recombination deficiency validated across laboratories, PAOLA-1 / ENGOT-ov25, Homologous recombination deficiency (HRD) in breast cancer.
Shares Ovarian Cancer Research Alliance (OCRA), A functional test for homologous recombination deficiency validated across laboratories, PRIMA / ENGOT-OV26, PAOLA-1 / ENGOT-ov25.
Shares Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters, RAD51 foci assay (functional HRD test), Genome-wide loss of heterozygosity (gLOH), Base excision repair, PARP & alkylation damage.
Shares PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations, TRITON3: rucaparib or physician's choice in metastatic castration-resistant prostate cancer, Genome-wide loss of heterozygosity (gLOH), TRITON2: rucaparib in men with metastatic castration-resistant prostate cancer harbouring a BRCA1 or BRCA2 alteration.