# Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis

Source: https://onco.cc/key-papers/paper-cortazar-ctneobc-pcr-pooled-analysis-lancet-2014/  
OnCo record `paper-cortazar-ctneobc-pcr-pooled-analysis-lancet-2014` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: tnbc-evidence
- Journal: The Lancet
- Year: 2014
- DOI: 10.1016/S0140-6736(13)62422-8
- Authors: Cortazar P, Zhang L, Untch M, et al.
- 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).
- What it means: 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.

## Sources

- Lancet 2014: https://doi.org/10.1016/S0140-6736(13)62422-8
- PubMed: https://pubmed.ncbi.nlm.nih.gov/24529560/

## Connected records

- key papers: [Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer](https://onco.cc/key-papers/paper-liedtke-neoadjuvant-response-survival-tnbc-jco-2008/)
- cancers: [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- terms: [Event-free / disease-free survival (EFS, DFS, iDFS, RFS)](https://onco.cc/terms/efs/), [Hazard ratio (HR)](https://onco.cc/terms/hazard-ratio/), [Overall survival (OS)](https://onco.cc/terms/os/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/)
- bottlenecks: [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [The Lancet](https://onco.cc/journals/lancet/)
- roadmaps: [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- ideas: [Give exceptional responders less: pembrolizumab omission after complete response, anthracycline-free regimens and chemotherapy omission in lymphocyte-rich stage I disease](https://onco.cc/ideas/idea-tnbc-de-escalation-for-exceptional-responders/)

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