Meeting
2014 ASCO Annual Meeting
Prognostic and predictive significance of PAM50 intrinsic subtypes in the NCIC CTG MA.21 phase III chemotherapy trial.
Authors
Karen A. Gelmon
British Columbia Cancer Agency, Vancouver, BC, Canada
Karen A. Gelmon , Judy-Anne W. Chapman , Shuzhen Liu , Margot J. Burnell , Mark Norman Levine , Kathleen I. Pritchard , Timothy Joseph Whelan , Hope S. Rugo , Kathy S. Albain , Edith A. Perez , Shakeel Virk , Patti O'Brien , Lois E. Shepherd , Torsten O. Nielsen
Organizations
British Columbia Cancer Agency, Vancouver, BC, Canada, NCIC Clinical Trials Group, Queen's University, Kingston, ON, Canada, Vancouver Coastal Health Research Institute and University of British Columbia, Vancouver, BC, Canada, Saint John Regional Hospital, Saint John, NB, Canada, Ontario Clinical Oncology Group, McMaster University, Hamilton, ON, Canada, Sunnybrook Odette Cancer Centre and the University of Toronto, Toronto, ON, Canada, Juravinski Cancer Centre, Hamilton, ON, Canada, University of California San Francisco Comprehensive Cancer Center, San Francisco, CA, Loyola University Medical Center, Maywood, IL, Mayo Clinic, Jacksonville, FL, NCIC Clinical Trials Group, Kingston, ON, Canada, NCIC, Kingson, ON, Canada
Research Funding
Other
Background: Breast cancer intrinsic subtypes defined by the 50-gene PAM50 test were reported to be prognostic and predictive in endocrine therapy trials. MA21 randomized 2,104 patients to receive dose intense cyclophosphamide, epirubicin and flurouracil (CEF); dose dense, dose intense epirubicin, cyclophosphamide and paclitaxel (EC/T); or 3-weekly doxorubicin, cyclophosphamide and paclitaxel (AC/T). We previously reported that AC/T had reduced relapse free survival (RFS) compared to both CEF and EC/T. Here, we investigated the prognostic and predictive (taxane versus not) significance of PAM50 in MA.21. Methods: Patients were ≤60 years old with node-positive or high-risk node-negative breast cancer. Median follow-up was 8 years. Intrinsic subtypes (luminal A, luminal B, basal-like, HER2E) were determined with FFPE extracted total RNA by Nanostring PAM50. Univariate assessment was with a stratified log-rank test. Effects of intrinsic subtypes and baseline patient characteristics on relapse-free survival (RFS) were investigated with stratified step-wise Cox multivariate regression, adding a factor if p<0.05. Results: The 1,094 cases completing PAM50 intrinsic subtyping were not significantly (p<0.05) different compared to those who did not in terms of treatment and stratification factors. 27% were classified as luminal A; 23% luminal B; 32% basal-like; and 18% HER2E. Intrinsic subtypes had a significant (p<0.001) univariate association with RFS. In multivariate analyses, intrinsic subtype had a significant prognostic effect on RFS (p= 0.001). Compared with luminal A, the hazard ratios (HR) were: luminal B =1.47 (95% CI = 0.93-2.30, p=0.10); basal-like= 1.95 (CI = 1.10-3.47, p=0.02); and HER2E = 2.66 (95% CI = 1.63-4.34, p<0.001). The interaction term between intrinsic subtype and treatment was not significant (p>0.05). Conclusions: Intrinsic subtype defined by the Nanostring PAM50 test had a significant prognostic effect on RFS for breast cancer patients treated with CEF, EC/T and AC/T. Subtype was not predictive of outcome amongst these chemotherapy regimens. Clinical trial information: NCT00014222.
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Abstract Details
Session Type
Poster Highlights Session
Session Title
Tumor Biology
Track
Tumor Biology
Sub Track
Molecular Diagnostics and Imaging
Clinical Trial Registration Number
NCT00014222
Citation
J Clin Oncol 32:5s, 2014 (suppl; abstr 11019)
DOI
10.1200/jco.2014.32.15_suppl.11019
Abstract #
11019
Poster Bd #
8
Abstract Disclosures
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