{"entity":{"id":"hrd-in-breast-cancer","kind":"term","name":"Homologous recombination deficiency (HRD) in breast cancer","aka":["HRD score in breast cancer","HRD in TNBC","Genomic instability score 42","HR-deficient triple-negative breast cancer","BRCAness"],"tldr":"Homologous recombination deficiency means a tumour cannot mend double-strand DNA breaks properly, most often because BRCA1 or BRCA2 is lost. About seven in ten triple-negative tumours score as deficient, and they respond better to platinum chemotherapy; but unlike ovarian cancer, no breast cancer drug is approved on the basis of an HRD score, only on a germline BRCA result.","summary":"Three DNA-based measures of genomic instability (loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions) are summed into an HRD score, with deficiency defined as a score of 42 or more or a BRCA1/2 mutation. In three neoadjuvant platinum trials in triple-negative disease, HR deficiency predicted residual cancer burden 0 or I and pathological complete response (odds ratios 4.96 and 6.52 in the platinum, gemcitabine and iniparib trial; 10.18 and 17.00 in two cisplatin trials), remained significant after adjustment for clinical variables, and identified responders among BRCA1/2 non-mutated tumours (Telli 2016). In GeparSixto, HRD was measured in 193 of 315 triple-negative participants: 136 (70.5 percent) were HR deficient, 82 of them (60.3 percent) with a high score but no tumour BRCA mutation; HR deficiency independently predicted pathological complete response (odds ratio 2.60), and adding carboplatin raised the rate from 33.9 to 63.5 percent in HR-deficient tumours but only from 20.0 to 29.6 percent in non-deficient tumours, with the interaction test not significant, so HRD predicted response but not carboplatin benefit; carboplatin improved disease-free survival in triple-negative disease overall (hazard ratio 0.56) (Loibl 2018). Beyond germline BRCA, olaparib produced confirmed responses in metastatic breast cancer with germline PALB2 mutations (objective response 82 percent, median progression-free survival 13.3 months) and somatic BRCA1/2 mutations (50 percent, 6.3 months) but none with ATM or CHEK2 mutations alone (TBCRC 048, Tung 2020). Regulatory use differs from ovarian cancer: NICE's adjuvant olaparib recommendation rests on a germline BRCA mutation (TA886), not an HRD score, and the platinum recommendation in NG101 1.8 applies to all triple-negative disease needing neoadjuvant chemotherapy, HRD-tested or not. The site's general HRD term and the hrd-positive readout carry the ovarian thresholds and assays.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Homologous_recombination","links":[{"label":"Telli, Clin Cancer Res 2016: HRD score predicts response to platinum neoadjuvant chemotherapy in triple-negative breast cancer","url":"https://doi.org/10.1158/1078-0432.ccr-15-2477"},{"label":"Loibl, Ann Oncol 2018: GeparSixto survival and HRD score as predictor of response","url":"https://doi.org/10.1093/annonc/mdy460"},{"label":"Tung, J Clin Oncol 2020: TBCRC 048, olaparib for metastatic breast cancer with germline PALB2 or somatic BRCA mutations","url":"https://doi.org/10.1200/jco.20.02151"},{"label":"NICE TA886: olaparib for adjuvant treatment of BRCA mutation-positive HER2-negative high-risk early breast cancer (May 2023)","url":"https://www.nice.org.uk/guidance/ta886"},{"label":"NICE NG101: early and locally advanced breast cancer (receptor testing 1.3, genetic testing 1.3.6, triple-negative section 1.8)","url":"https://www.nice.org.uk/guidance/ng101/chapter/Recommendations"}],"tags":["breast","tnbc"],"related":[],"cancers":["tnbc","brca-associated-tnbc","tnbc-early"],"sections":[],"technologies":["hrd-testing","platinum","parp-inhibitor"],"targets":["brca","parp"],"drugs":["carboplatin","olaparib"],"companies":[],"institutions":[],"pathways":[],"terms":["hrd","germline-vs-somatic","pcr","rcb"],"trials":["geparsixto"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},"route":"/terms/hrd-in-breast-cancer/","neighbours":{"cancer":[{"id":"tnbc-basal-like-1","kind":"cancer","name":"Basal-like 1 triple-negative breast cancer (BL1)","route":"/cancers/tnbc-basal-like-1/"},{"id":"brca-associated-tnbc","kind":"cancer","name":"BRCA-associated triple-negative breast cancer","route":"/cancers/brca-associated-tnbc/"},{"id":"tnbc-early","kind":"cancer","name":"Early triple-negative breast cancer","route":"/cancers/tnbc-early/"},{"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":"parp-inhibitor","kind":"technology","name":"PARP inhibitors","route":"/technologies/parp-inhibitor/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"}],"target":[{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"parp","kind":"target","name":"PARP","route":"/targets/parp/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"olaparib","kind":"drug","name":"Olaparib","route":"/drugs/olaparib/"}],"term":[{"id":"exceptional-responder","kind":"term","name":"Exceptional responder","route":"/terms/exceptional-responder/"},{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"},{"id":"rcb","kind":"term","name":"Residual cancer burden (RCB)","route":"/terms/rcb/"}],"trial":[{"id":"geparsixto","kind":"trial","name":"GeparSixto","route":"/trials/geparsixto/"}]}}