Response prediction to neoadjuvant chemotherapy: Comparison between pretherapeutic gene expression profiles and in vitro chemosensitivity assay.

Abstract

Although the use of (neo-)adjuvant chemotherapy in breast cancer patients has resulted in improved outcome, not all patients benefit equally. We have evaluated the utility of an in vitro chemosensitivity assay in predicting response to neoadjuvant chemotherapy. Pre-therapeutic biopsies were obtained from 30 breast cancer patients assigned to neoadjuvant epirubicin 75 mg/m2 and docetaxel 75 mg/m2 (Epi/Doc) in a prospectively randomized clinical trial. Biopsies were subjected to a standardized ATP-based Epi/Doc chemosensitivity assay, and to gene expression profiling. Patients then received 3 cycles of chemotherapy, and response was evaluated by changes in tumor diameter and Ki67 expression. The efficacy of Epi/Doc in vitro was correlated with differential changes in tumor cell proliferation in response to Epi/Doc in vivo (p = 0.0011; r = 0.73670, Spearmans rho), but did not predict for changes in tumor size. While a pre-therapeutic gene expression signature identified tumors with a clinical response to Epi/Doc, no such signature could be found for tumors that responded to Epi/Doc in vitro, or tumors in which Epi/Doc exerted an antiproliferative effect in vivo. This is the first prospective clinical trial to demonstrate the utility of a standardized in vitro chemosensitivity assay in predicting the individual biological response to chemotherapy in breast cancer.

Statistical methods applied to omics data

“…In this study, from 31 breast cancer tissues, differentially expressed genes were identified by the significance analysis of microarrays method using a false discovery rate of 0.05. Singer et al [24] have evaluated the utility of an in-vitro chemosensitivity assay in predicting response to neoadjuvant epirubicin and docetaxel in 30 patients. Korde et al [16] examined changes in genes associated with neoadjuvant docetaxel and capecitabine using pre/post treatment biopsies collected in 21 patients.…”