Evaluation of the performance of breast cancer cell line–derived multigene predictors of chemotherapy response in multiple clinical trials.

64 Background: While various multi-gene predictors (MGPs) of chemotherapy response have been developed based on cancer patient primary tissues or cancer cell-lines, the accuracy and consistency of these predictors remain a concern in clinical validation studies. In this study we developed four unique MGPs for chemotherapy response from breast cancer cell lines and performed a systematic evaluation of the performance of these MGPs using data from five distinct clinical trials. Methods: Forty-six immortalized breast cancer cell-lines were exposed to various concentrations of drug combinations [paclitaxel, 5-fluorouracil, doxorubicin, cyclophosphamide (TFAC); 5-fluorouracil, doxorubicin, cyclophosphamide (FAC); 5-fluorouracil, epirubicin, cyclophosphamide (FEC) and epirubicin, cyclophosphamide (EC)] using an in vitro chemosensitivity assay. Utilizing publicly available breast cancer cell-line microarray data, genes highly associated with in vitro chemosensitivity were selected as candidate MGPs. Five indepen...