Predicting response and survival in chemotherapy-treated triple-negative breast cancer

A. Prat, A. Lluch, J. Albanell, W. T. Barry, C. Fan, J. I. Chacón, J. S. Parker, L. Calvo, A. Plazaola, A. Arcusa, M. A. Seguí-Palmer, O. Burgues, N. Ribelles, A. Rodriguez-Lescure, A. Guerrero, M. Ruiz-Borrego, B. Munarriz, J. A. López, B. Adamo, M. C.U. CheangY. Li, Z. Hu, M. L. Gulley, M. J. Vidal, B. N. Pitcher, M. C. Liu, M. L. Citron, M. J. Ellis, E. Mardis, T. Vickery, C. A. Hudis, E. P. Winer, L. A. Carey, R. Caballero, E. Carrasco, M. Martín, C. M. Perou, E. Alba

Research output: Contribution to journalReview article

60 Scopus citations

Abstract

Background: In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC).

Methods: Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated.

Results: Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival.

Conclusions: The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not.

Original languageEnglish (US)
Pages (from-to)1532-1541
Number of pages10
JournalBritish journal of cancer
Volume111
Issue number8
DOIs
StatePublished - Oct 14 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Predicting response and survival in chemotherapy-treated triple-negative breast cancer'. Together they form a unique fingerprint.

  • Cite this

    Prat, A., Lluch, A., Albanell, J., Barry, W. T., Fan, C., Chacón, J. I., Parker, J. S., Calvo, L., Plazaola, A., Arcusa, A., Seguí-Palmer, M. A., Burgues, O., Ribelles, N., Rodriguez-Lescure, A., Guerrero, A., Ruiz-Borrego, M., Munarriz, B., López, J. A., Adamo, B., ... Alba, E. (2014). Predicting response and survival in chemotherapy-treated triple-negative breast cancer. British journal of cancer, 111(8), 1532-1541. https://doi.org/10.1038/bjc.2014.444