Cumulative incidence plots showing "High LRR risk" patients of the training set stratified according to PMRT and tumorsize (A), lymph node positive status (B), ER status (C) and combinations of tumorsize and nodal status (D), respectively.
ARTICLE ABSTRACT
Purpose: To identify genes predicting benefit of radiotherapy in patients with high-risk breast cancer treated with systemic therapy and randomized to receive or not receive postmastectomy radiotherapy (PMRT).Experimental Design: The study was based on the Danish Breast Cancer Cooperative Group (DBCG82bc) cohort. Gene-expression analysis was performed in a training set of frozen tumor tissue from 191 patients. Genes were identified through the Lasso method with the endpoint being locoregional recurrence (LRR). A weighted gene-expression index (DBCG-RT profile) was calculated and transferred to quantitative real-time PCR (qRT-PCR) in corresponding formalin-fixed, paraffin-embedded (FFPE) samples, before validation in FFPE from 112 additional patients.Results: Seven genes were identified, and the derived DBCG-RT profile divided the 191 patients into “high LRR risk” and “low LRR risk” groups. PMRT significantly reduced risk of LRR in “high LRR risk” patients, whereas “low LRR risk” patients showed no additional reduction in LRR rate. Technical transfer of the DBCG-RT profile to FFPE/qRT-PCR was successful, and the predictive impact was successfully validated in another 112 patients.Conclusions: A DBCG-RT gene profile was identified and validated, identifying patients with very low risk of LRR and no benefit from PMRT. The profile may provide a method to individualize treatment with PMRT. Clin Cancer Res; 20(20); 5272–80. ©2014 AACR.
