{"entity":{"id":"paper-hahnen-geparsixto-germline-brca-jama-oncol-2017","kind":"paper","name":"Germline mutation status, pathological complete response, and disease-free survival in triple-negative breast cancer: secondary analysis of the GeparSixto randomized clinical trial","aka":[],"tldr":"In GeparSixto, 17% of triple-negative patients carried a germline BRCA1 or BRCA2 mutation; they responded well to chemotherapy whether or not carboplatin was added, while it was the non-carriers whose complete response rate rose from 36% to 55% with carboplatin.","summary":"Archived DNA from 291 of 315 TNBC patients in GeparSixto (NCT01426880) was analysed for germline mutations in BRCA1, BRCA2 and 16 other predisposition genes. Pathological complete response (ypT0/is ypN0) was 56.8% with carboplatin and 41.4% without (OR 1.87). Pathogenic BRCA1/2 germline mutations were present in 50 patients (17.2%). Without carboplatin, pCR was 66.7% in carriers versus 36.4% in non-carriers (OR 3.50); carboplatin did not raise the carriers' rate further (65.4%) but raised non-carriers' from 36.4% to 55% (OR 2.14), and non-carriers gained disease-free survival with carboplatin (85.3% versus 73.5%; HR 0.53).","asOf":"2026-09-24","links":[{"label":"Hahnen et al., JAMA Oncol 2017: germline status and response in 291 GeparSixto TNBC patients","url":"https://doi.org/10.1001/jamaoncol.2017.1007"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28715532/"}],"tags":[],"related":[],"cancers":["tnbc","tnbc-early"],"sections":[],"technologies":[],"targets":["brca"],"drugs":["carboplatin"],"companies":["gbg"],"institutions":[],"pathways":[],"terms":["gbrca-mutation","pcr"],"trials":["geparsixto"],"people":["sibylle-loibl","carsten-denkert","rita-schmutzler"],"bottlenecks":[],"keyPapers":[],"journals":["jama-oncology"],"dependsOn":[],"notes":[],"journal":"JAMA Oncology","year":2017,"doi":"10.1001/jamaoncol.2017.1007","pmid":"28715532","authors":"Hahnen E, Lederer B, Hauke J, et al.","paperType":"rct","findings":["Germline BRCA1/2 in 50 of 291 TNBC patients, 17.2%.","Carriers: pCR 66.7% without and 65.4% with carboplatin; non-carriers: 36.4% rising to 55%.","Non-carriers gained disease-free survival with carboplatin (HR 0.53)."],"whatItMeans":"Germline status changes the reading of the platinum question: in early TNBC the carboplatin benefit was seen in non-carriers, so a BRCA result argues for testing everyone rather than reserving platinum for carriers.","caveats":["Secondary analysis of a non-standard regimen with bevacizumab and liposomal doxorubicin.","Small carrier subgroups (24 and 26 patients)."],"changedPractice":false,"participants":291},"route":"/key-papers/paper-hahnen-geparsixto-germline-brca-jama-oncol-2017/","neighbours":{"cancer":[{"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/"}],"target":[{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"}],"company":[{"id":"gbg","kind":"company","name":"German Breast Group (GBG)","route":"/companies/gbg/"}],"term":[{"id":"gbrca-mutation","kind":"term","name":"Germline BRCA mutation (gBRCA)","route":"/terms/gbrca-mutation/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"}],"trial":[{"id":"geparsixto","kind":"trial","name":"GeparSixto","route":"/trials/geparsixto/"}],"person":[{"id":"carsten-denkert","kind":"person","name":"Carsten Denkert","route":"/people/carsten-denkert/"},{"id":"rita-schmutzler","kind":"person","name":"Rita Schmutzler","route":"/people/rita-schmutzler/"},{"id":"sibylle-loibl","kind":"person","name":"Sibylle Loibl","route":"/people/sibylle-loibl/"}],"journal":[{"id":"jama-oncology","kind":"journal","name":"JAMA Oncology","route":"/journals/jama-oncology/"}],"biomarker":[{"id":"brca-germline","kind":"biomarker","name":"Germline BRCA1/2 pathogenic variant (gBRCAm)","route":"/biomarkers/brca-germline/"}]}}