Radiation-induced gene signature predicts pathologic complete response to neoadjuvant chemotherapy in breast cancer patients

Abstract

The identification of biomarkers predictive of neoadjuvant chemotherapy response in breast cancer patients would be an important advancement in personalized cancer therapy. In this study, we hypothesized that due to similarities between radiation-and chemotherapy-induced cellular response mechanisms, radiation-responsive genes may be useful in predicting response to neoadjuvant chemotherapy. Murine p53 null breast cancer cell lines representative of the luminal, basal-like and claudin-low human breast cancer subtypes were irradiated to identify radiation-responsive genes across subtypes. These murine tumor radiation-induced genes were then converted to their human orthologs, and subsequently tested as a predictor of pathologic complete response (pCR), which was validated on two independent published neoadjuvant chemotherapy datasets of genomic data with chemotherapy response. A radiation-induced gene signature consisting of 30 genes was identified on a training set of 337 human primary breast cancer tumor samples that was prognostic for survival. Mean expression of this signature was calculated for individual samples on two independent published datasets and was found to be significantly predictive of pCR. Multivariate logistic regression analysis in both independent datasets showed that this 30 gene signature added significant predictive information independent of that provided by standard clinical predictors and other gene expression-based predictors of pCR. This study provides new information for radiation-induced biology, as well as information regarding response to neoadjuvant chemotherapy and a possible means of improving the prediction of pCR. © 2014 by Radiation Research Society.