PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer

Miguel Martín, Aleix Prat, Álvaro Rodríguez-Lescure, Rosalía Caballero, Mark T.W. Ebbert, Blanca Munárriz, Manuel Ruiz-Borrego, Roy R.L. Bastien, Carmen Crespo, Carole Davis, César A. Rodríguez, José M. López-Vega, Vicente Furió, Ana M. García, Maribel Casas, Matthew J. Ellis, Donald A. Berry, Brandelyn N. Pitcher, Lyndsay Harris, Amparo RuizEric Winer, Clifford Hudis, Inge J. Stijleman, David P. Tuck, Eva Carrasco, Charles M. Perou, Philip S. Bernard

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The predictive value of PAM50 subtypes and the 11-gene proliferation score contained within the PAM50 assay were evaluated in 820 patients from the GEICAM/9906 randomized phase III trial comparing adjuvant FEC to FEC followed by weekly paclitaxel (FEC-P). Multivariable Cox regression analyses of the secondary endpoint of overall survival (OS) were performed to determine the significance of the interaction between treatment and the (1) PAM50 subtypes, (2) PAM50 proliferation score, and (3) clinical and pathological variables. Similar OS analyses were performed in 222 patients treated with weekly paclitaxel versus paclitaxel every 3 weeks in the CALGB/9342 and 9840 metastatic clinical trials. In GEICAM/9906, with a median follow up of 8.7 years, OS of the FEC-P arm was significantly superior compared to the FEC arm (unadjusted HR = 0.693, p = 0.013). A benefit from paclitaxel was only observed in the group of patients with a low PAM50 proliferation score (unadjusted HR = 0.23, p < 0.001; and interaction test, p = 0.006). No significant interactions between treatment and the PAM50 subtypes or the various clinical-pathological variables, including Ki-67 and histologic grade, were identified. Finally, similar OS results were obtained in the CALGB data set, although the interaction test did not reach statistical significance (p = 0.109). The PAM50 proliferation score identifies a subset of patients with a low proliferation status that may derive a larger benefit from weekly paclitaxel.

Original languageEnglish
Pages (from-to)457-466
Number of pages10
JournalBreast Cancer Research and Treatment
Volume138
Issue number2
DOIs
StatePublished - Apr 2013

Bibliographical note

Funding Information:
Acknowledgments The authors would like to thank Torsten O. Nielsen of the Genetic Pathology Evaluation Centre, Vancouver Coastal Health Research Institute, British Columbia Cancer Agency, and University of British Columbia, Vancouver, Canada, for his critical review of the manuscript. Funding for M Martin was also supported by FEDER (RETICC-RD12/0036/0076). Funding for MJ Ellis, CM Perou, and PS Bernard was supported by the National Cancer Institute (NCI) Strategic Partnering to Evaluate Cancer Signatures Grant CA114722-01, and CM Perou was also supported by the NCI Breast SPORE program (P50-CA58223-09A1) and the Breast Cancer Research Foundation. Funding for L. Harris was supported by the National Institute of Health (NIH) Research Project Grant Program (R01). A Prat is supported by a grant from the Sociedad Es-pañola de Oncología Médica (SEOM), and is affiliated to the Medicine PhD program of the Autonomous University of Barcelona (UAB), Spain.

Keywords

  • Breast cancer
  • PAM50 proliferation score
  • PAM50 subtypes
  • Paclitaxel
  • Prediction of paclitaxel efficacy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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