There is an unmet clinical need to identify biomarkers for breast cancer neoadjuvant chemotherapy. Here, using miRNA TaqMan Low-Density Arrays (TLDA), we analyzed the miRNA expression profile in pre-treatment needle aspiration tumor samples from patients who received taxane-anthracycline-based neoadjuvant chemotherapy. Although, in an unsupervised hierarchical cluster analysis, the total miRNA expression profile could not generate a tree with clear distinction between pathologic complete response (pCR) and non-pCR classes, we found that elevated expression of miR-125b and miR-141 was associated with non-pCR. In vitro experiments indicated that inhibition of miR-125b and miR-141 expression reduced cellular survival in response to taxane-anthracycline treatment. Furthermore, co-transfection with miR-125b and miR-141 mimics increased resistance of MCF7 and BT549 cells to taxane-anthracycline induced cytotoxicity. Pathway analyses indicated that many of the target proteins of miR-125b are involved in apoptotic pathways and cell cycle control. Together, we provide evidence that elevated miR-125b and 141 expression predicts a poor clinical responsiveness of taxane-anthracycline-based neoadjuvant chemotherapy.
Keywords: breast cancer; microRNA; neoadjuvant chemotherapy; pathologic complete response; predictive biomarkers..