Ontology highlight
ABSTRACT: Background
National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31 suggested the efficacy of adjuvant trastuzumab, even in HER2-negative breast cancer. This finding prompted us to develop a predictive model for degree of benefit from trastuzumab using archived tumor blocks from B-31.Methods
Case subjects with tumor blocks were randomly divided into discovery (n = 588) and confirmation cohorts (n = 991). A predictive model was built from the discovery cohort through gene expression profiling of 462 genes with nCounter assay. A predefined cut point for the predictive model was tested in the confirmation cohort. Gene-by-treatment interaction was tested with Cox models, and correlations between variables were assessed with Spearman correlation. Principal component analysis was performed on the final set of selected genes. All statistical tests were two-sided.Results
Eight predictive genes associated with HER2 (ERBB2, c17orf37, GRB7) or ER (ESR1, NAT1, GATA3, CA12, IGF1R) were selected for model building. Three-dimensional subset treatment effect pattern plot using two principal components of these genes was used to identify a subset with no benefit from trastuzumab, characterized by intermediate-level ERBB2 and high-level ESR1 mRNA expression. In the confirmation set, the predefined cut points for this model classified patients into three subsets with differential benefit from trastuzumab with hazard ratios of 1.58 (95% confidence interval [CI] = 0.67 to 3.69; P = .29; n = 100), 0.60 (95% CI = 0.41 to 0.89; P = .01; n = 449), and 0.28 (95% CI = 0.20 to 0.41; P < .001; n = 442; P(interaction) between the model and trastuzumab < .001).Conclusions
We developed a gene expression-based predictive model for degree of benefit from trastuzumab and demonstrated that HER2-negative tumors belong to the moderate benefit group, thus providing justification for testing trastuzumab in HER2-negative patients (NSABP B-47).
SUBMITTER: Pogue-Geile KL
PROVIDER: S-EPMC3848987 | biostudies-literature | 2013 Dec
REPOSITORIES: biostudies-literature
Pogue-Geile Katherine L KL Kim Chungyeul C Jeong Jong-Hyeon JH Tanaka Noriko N Bandos Hanna H Gavin Patrick G PG Fumagalli Debora D Goldstein Lynn C LC Sneige Nour N Burandt Eike E Taniyama Yusuke Y Bohn Olga L OL Lee Ahwon A Kim Seung-Il SI Reilly Megan L ML Remillard Matthew Y MY Blackmon Nicole L NL Kim Seong-Rim SR Horne Zachary D ZD Rastogi Priya P Fehrenbacher Louis L Romond Edward H EH Swain Sandra M SM Mamounas Eleftherios P EP Wickerham D Lawrence DL Geyer Charles E CE Costantino Joseph P JP Wolmark Norman N Paik Soonmyung S
Journal of the National Cancer Institute 20131121 23
<h4>Background</h4>National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31 suggested the efficacy of adjuvant trastuzumab, even in HER2-negative breast cancer. This finding prompted us to develop a predictive model for degree of benefit from trastuzumab using archived tumor blocks from B-31.<h4>Methods</h4>Case subjects with tumor blocks were randomly divided into discovery (n = 588) and confirmation cohorts (n = 991). A predictive model was built from the discovery cohort through ...[more]