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. Cheang; Y. 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

doi:10.1038/bjc.2014.444

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

Medical Oncology

Research output: Contribution to journal › Review article › peer-review

71 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 language	English (US)
Pages (from-to)	1532-1541
Number of pages	10
Journal	British journal of cancer
Volume	111
Issue number	8
DOIs	https://doi.org/10.1038/bjc.2014.444
State	Published - Oct 14 2014

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1038/bjc.2014.444

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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

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

@article{42c5dc90a7f14a68afff3f09265f1546,

title = "Predicting response and survival in chemotherapy-treated triple-negative breast cancer",

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, {M. 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",

year = "2014",

month = oct,

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doi = "10.1038/bjc.2014.444",

language = "English (US)",

volume = "111",

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number = "8",

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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, M. 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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U2 - 10.1038/bjc.2014.444

DO - 10.1038/bjc.2014.444

M3 - Review article

C2 - 25101563

AN - SCOPUS:84908893016

SN - 0007-0920

VL - 111

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EP - 1541

JO - British journal of cancer

JF - British journal of cancer

IS - 8

ER -

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

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