Homologous recombination deficiency (HRD)
A tumour that cannot properly repair double-strand DNA breaks, usually because of BRCA or related gene loss.
Detected by BRCA1/2 mutation or genomic-scar scores (myChoice CDx GIS ≥42, FoundationOne LOH). Predicts PARP inhibitor and platinum benefit. About 50% of high-grade serous ovarian and 20-30% of TNBC.
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.
Every woman diagnosed with advanced high-grade ovarian cancer should be tested for BRCA mutations at diagnosis, because those who carry one should receive two years of olaparib after chemotherapy, which greatly extends the time in remission and improves long-term survival. The plateau in the survival curves suggests some patients are cured by this approach. Toxicity is mostly anaemia, fatigue and nausea, and the two-year limit appears sufficient.
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not linked directly; found by shared links- TechnologyPARP inhibitors
Shares Ovarian Cancer Research Alliance (OCRA), A functional test for homologous recombination deficiency validated across laboratories, Rucaparib, Germline BRCA mutation (gBRCA).
- ProductOlaparib
Shares PARP inhibitor + bevacizumab maintenance (HRD-positive), A functional test for homologous recombination deficiency validated across laboratories, PAOLA-1 / ENGOT-ov25, Germline BRCA mutation (gBRCA).
- PathwayDNA damage response & homologous recombination
Shares HRD & BRCA testing, Enabling characteristic: genome instability and mutation, Mutagenesis & mutational signatures, Base excision repair, PARP & alkylation damage.
- ProductNiraparib
Shares PRIMA / ENGOT-OV26, ARCAGY-GINECO, Base excision repair, PARP & alkylation damage, Synthetic lethality: paired dependencies.
- TechnologyRisk-reducing and opportunistic salpingectomy
Shares Ovarian Cancer Research Alliance (OCRA), High-grade serous ovarian carcinoma (HGSOC), Inherited risk is mostly unidentified, BRCA1 / BRCA2 (HRD).
- ProductTalazoparib
Shares Base excision repair, PARP & alkylation damage, Synthetic lethality: paired dependencies, Double-strand break repair: HR versus end joining, PARP.
- TargetATR
Shares Enabling characteristic: genome instability and mutation, Base excision repair, PARP & alkylation damage, Synthetic lethality: paired dependencies, Double-strand break repair: HR versus end joining.
- PathwayDNA replication stress
Shares Enabling characteristic: genome instability and mutation, Base excision repair, PARP & alkylation damage, Synthetic lethality: paired dependencies, Double-strand break repair: HR versus end joining.