10597 Background: IR is associated with adverse outcome in breast cancer. IR may affect patient outcome via the insulin and the IGF axis, acting through the tyrosine kinase signaling in enhancing cell proliferation. To date, no study explored the role of insulin- related gene expression in breast cancer progression. The aim of this study was to evaluate the prognostic value of a set of insulin-related genes using published microarray datasets. Methods: IR genes were sorted according to the “insulin sensitivity gene set” previously defined in peripheral tissues of healthy subjects screened for IR by the euglycaemic insulin clamp technique. One-hundred-forty- three genes were used to develop an outcome predictor on a training set of 102 primary breast tumors, randomly selected from 159 patients in the GEO database ( GSE1456 ). The outcome predictor was validated on the remaining 57 patients. Primary outcome measure was relapse free survival (RFS). Univariate non-parametric Mann-Whitney U test was used to identify genes differentially expressed. Expression of genes significantly correlated with relapse was combined in a linear score. Patients were classified as low or high risk with respect to the median score. Kaplan-Meier curves were used to evaluate the discriminating power of the score. Results: Fourteen genes resulted differentially expressed in the training set: the 8-year RFS was 91% (SE =4%) and 51% (SE = 8%) in the low risk and high risk group, respectively (p < .001). In the validation set, the 8-year RFS was 97% (SE = 3%) and 54% (SE = 10%), respectively (p = .009), supporting the discriminating ability of the score. By multivariate Cox analysis, the prognostic ability of the score was independent of subtype and grade (p < .001). Conclusions: Our data provide the first evidence that expression of insulin related genes can predict outcome, and indicate that the insulin pathway is involved in breast cancer progression. This is particularly important since IR is responsive to lifestyle interventions. We are currently validating the insulin-related score on independent breast cancer microarray datasets. No significant financial relationships to disclose.
Multiple forms of BRMS1 are differentially expressed in the MCF10 isogenic breast cancer progression model
