{"entity":{"id":"paper-cortazar-ctneobc-pcr-pooled-analysis-lancet-2014","kind":"paper","name":"Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis","aka":[],"tldr":"The US regulator's pooled analysis of 11,955 patients in 12 trials that found complete disappearance of the tumour before surgery predicts survival most strongly in triple-negative disease, but that a trial raising the complete response rate does not reliably improve survival.","summary":"Cortazar, Zhang, Untch, Mehta and colleagues pooled 12 international neoadjuvant trials with at least 200 patients, response and survival data and three years of follow-up (11,955 patients), comparing three definitions of pathological complete response and testing trial-level surrogacy. Eradication from breast and nodes (ypT0 ypN0, or ypT0/is ypN0) associated better with event-free survival (hazard ratios 0.44 and 0.48) and overall survival (0.36 for both) than eradication from the breast alone (0.60 and 0.51). The association was strongest in triple-negative breast cancer (event-free survival hazard ratio 0.24, 95 percent confidence interval 0.18 to 0.33; overall survival 0.16, 0.11 to 0.25) and in HER2-positive, hormone receptor-negative disease treated with trastuzumab. At trial level there was little association between increases in pathological complete response and event-free (R squared 0.03) or overall survival (0.24), so the analysis could not validate pathological complete response as a surrogate endpoint.","asOf":"2026-09-24","links":[{"label":"Lancet 2014","url":"https://doi.org/10.1016/S0140-6736(13)62422-8"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24529560/"}],"tags":["tnbc-evidence"],"related":["paper-liedtke-neoadjuvant-response-survival-tnbc-jco-2008"],"cancers":["tnbc","breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["pcr","efs","os","hazard-ratio"],"trials":[],"people":[],"bottlenecks":["b-trial-design"],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2014,"doi":"10.1016/S0140-6736(13)62422-8","pmid":"24529560","authors":"Cortazar P, Zhang L, Untch M, et al.","paperType":"meta-analysis","findings":["Pathological complete response (ypT0/is ypN0) in triple-negative disease: event-free survival hazard ratio 0.24 (95 percent CI 0.18 to 0.33); overall survival 0.16 (0.11 to 0.25).","Trial-level association between pathological complete response gains and survival weak: R squared 0.03 (event-free) and 0.24 (overall)."],"whatItMeans":"The basis of the US accelerated approval pathway on pathological complete response that KEYNOTE-522 and neoadjuvant trials since have used, together with the warning that a higher response rate in a trial is a promise, not a proof, of longer life.","caveats":["Pooled trials used varied regimens and definitions.","Trial-level surrogacy tested across only 12 trials."],"changedPractice":true,"participants":11955},"route":"/key-papers/paper-cortazar-ctneobc-pcr-pooled-analysis-lancet-2014/","neighbours":{"paper":[{"id":"paper-liedtke-neoadjuvant-response-survival-tnbc-jco-2008","kind":"paper","name":"Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer","route":"/key-papers/paper-liedtke-neoadjuvant-response-survival-tnbc-jco-2008/"}],"cancer":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"term":[{"id":"efs","kind":"term","name":"Event-free / disease-free survival (EFS, DFS, iDFS, RFS)","route":"/terms/efs/"},{"id":"hazard-ratio","kind":"term","name":"Hazard ratio (HR)","route":"/terms/hazard-ratio/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"}],"bottleneck":[{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"journal":[{"id":"lancet","kind":"journal","name":"The Lancet","route":"/journals/lancet/"}],"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/"}],"idea":[{"id":"idea-tnbc-de-escalation-for-exceptional-responders","kind":"idea","name":"Give exceptional responders less: pembrolizumab omission after complete response, anthracycline-free regimens and chemotherapy omission in lymphocyte-rich stage I disease","route":"/ideas/idea-tnbc-de-escalation-for-exceptional-responders/"}]}}