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, Minetta 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

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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

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Triple Negative Breast Neoplasms
Drug Therapy
Survival
Logistic Models
Transcriptome
Proportional Hazards Models
Randomized Controlled Trials
Clinical Trials
Gene Expression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Prat, A., Lluch, A., Albanell, J., Barry, W. T., Fan, C., Chacón, J. I., ... 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

Predicting response and survival in chemotherapy-treated triple-negative breast cancer. / 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.; Cheang, M. C U; Li, Y.; Hu, Z.; Gulley, M. L.; Vidal, M. J.; Pitcher, B. N.; Liu, Minetta C; Citron, M. L.; Ellis, M. J.; Mardis, E.; Vickery, T.; Hudis, C. A.; Winer, E. P.; Carey, L. A.; Caballero, R.; Carrasco, E.; Martín, M.; Perou, C. M.; Alba, E.

In: British Journal of Cancer, Vol. 111, No. 8, 14.10.2014, p. 1532-1541.

Research output: Contribution to journalArticle

Prat, A, Lluch, A, Albanell, J, Barry, WT, Fan, C, Chacón, JI, Parker, JS, Calvo, L, Plazaola, A, Arcusa, A, Seguí-Palmer, MA, Burgues, O, Ribelles, N, Rodriguez-Lescure, A, Guerrero, A, Ruiz-Borrego, M, Munarriz, B, López, JA, Adamo, B, Cheang, MCU, Li, Y, Hu, Z, Gulley, ML, Vidal, MJ, Pitcher, BN, Liu, MC, Citron, ML, Ellis, MJ, Mardis, E, Vickery, T, Hudis, CA, Winer, EP, Carey, LA, Caballero, R, Carrasco, E, Martín, M, Perou, CM & Alba, E 2014, 'Predicting response and survival in chemotherapy-treated triple-negative breast cancer', British Journal of Cancer, vol. 111, no. 8, pp. 1532-1541. https://doi.org/10.1038/bjc.2014.444
Prat A, Lluch A, Albanell J, Barry WT, Fan C, Chacón JI et al. Predicting response and survival in chemotherapy-treated triple-negative breast cancer. British Journal of Cancer. 2014 Oct 14;111(8):1532-1541. https://doi.org/10.1038/bjc.2014.444
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. ; Cheang, M. C U ; Li, Y. ; Hu, Z. ; Gulley, M. L. ; Vidal, M. J. ; Pitcher, B. N. ; Liu, Minetta C ; Citron, M. L. ; Ellis, M. J. ; Mardis, E. ; Vickery, T. ; Hudis, C. A. ; Winer, E. P. ; Carey, L. A. ; Caballero, R. ; Carrasco, E. ; Martín, M. ; Perou, C. M. ; Alba, E. / Predicting response and survival in chemotherapy-treated triple-negative breast cancer. In: British Journal of Cancer. 2014 ; Vol. 111, No. 8. pp. 1532-1541.
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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.",
author = "A. Prat and A. Lluch and J. Albanell and Barry, {W. T.} and C. Fan and Chac{\'o}n, {J. I.} and Parker, {J. S.} and L. Calvo and A. Plazaola and A. Arcusa and Segu{\'i}-Palmer, {M. A.} and O. Burgues and N. Ribelles and A. Rodriguez-Lescure and A. Guerrero and M. Ruiz-Borrego and B. Munarriz and L{\'o}pez, {J. A.} and B. Adamo and Cheang, {M. C U} and Y. Li and Z. Hu and Gulley, {M. L.} and Vidal, {M. J.} and Pitcher, {B. N.} and Liu, {Minetta C} and Citron, {M. L.} and Ellis, {M. J.} and E. Mardis and T. Vickery and Hudis, {C. A.} and Winer, {E. P.} and Carey, {L. A.} and R. Caballero and E. Carrasco and M. Mart{\'i}n and Perou, {C. M.} and E. Alba",
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TY - JOUR

T1 - Predicting response and survival in chemotherapy-treated triple-negative breast cancer

AU - Prat, A.

AU - Lluch, A.

AU - Albanell, J.

AU - Barry, W. T.

AU - Fan, C.

AU - Chacón, J. I.

AU - Parker, J. S.

AU - Calvo, L.

AU - Plazaola, A.

AU - Arcusa, A.

AU - Seguí-Palmer, M. A.

AU - Burgues, O.

AU - Ribelles, N.

AU - Rodriguez-Lescure, A.

AU - Guerrero, A.

AU - Ruiz-Borrego, M.

AU - Munarriz, B.

AU - López, J. A.

AU - Adamo, B.

AU - Cheang, M. C U

AU - Li, Y.

AU - Hu, Z.

AU - Gulley, M. L.

AU - Vidal, M. J.

AU - Pitcher, B. N.

AU - Liu, Minetta C

AU - Citron, M. L.

AU - Ellis, M. J.

AU - Mardis, E.

AU - Vickery, T.

AU - Hudis, C. A.

AU - Winer, E. P.

AU - Carey, L. A.

AU - Caballero, R.

AU - Carrasco, E.

AU - Martín, M.

AU - Perou, C. M.

AU - Alba, E.

PY - 2014/10/14

Y1 - 2014/10/14

N2 - 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.

AB - 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.

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