{"entity":{"id":"platinum-plus-hrd","kind":"pairing","name":"Platinum chemotherapy in HRD tumours","aka":[],"tldr":"DNA-crosslinking chemotherapy is especially effective in tumours that cannot repair double-strand breaks.","summary":"This combination pairs Platinum agents with tumours carrying BRCA1 / BRCA2 (HRD) defects, because DNA-crosslinking chemotherapy is especially effective in cells that cannot repair double-strand breaks. The mechanism is that interstrand crosslinks need homologous recombination to repair, so HRD cells accumulate lethal double-strand breaks, as described in the DNA damage response & homologous recombination pathway. Multiple randomised trials support it: Carboplatin raises pathological complete response in Triple-negative breast cancer (TNBC) in GeparSixto and BrighTNess, with greater benefit in BRCA-mutant or HRD tumours. In Ovarian cancer, platinum sensitivity defines the treatable population, and the pairing is linked from the TNBC, Platinum agents and BRCA1 / BRCA2 (HRD) entries.","asOf":"2026-09-04","links":[{"label":"TNT trial: carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups (Nature Medicine 2018)","url":"https://doi.org/10.1038/s41591-018-0009-7"}],"tags":[],"related":[],"cancers":["tnbc","ovarian"],"sections":[],"technologies":[],"targets":[],"drugs":["carboplatin"],"companies":[],"institutions":[],"pathways":["ddr"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-tutt-nat-med"],"journals":[],"dependsOn":[],"notes":[],"a":"platinum","b":"brca","rationale":"Interstrand crosslinks need homologous recombination to repair; HRD cells accumulate lethal double-strand breaks.","evidence":"Multiple randomised trials.","pairingType":"combination"},"route":"/pairings/platinum-plus-hrd/","neighbours":{"cancer":[{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"}],"pathway":[{"id":"ddr","kind":"pathway","name":"DNA damage response & homologous recombination","route":"/pathways/ddr/"}],"paper":[{"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/"}],"technology":[{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"}],"target":[{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"}],"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/"}]}}