Subtype specific breast cancer event prediction

Abstract

We investigate the potential to enhance breast cancer event predictors by exploiting subtype information. We do this with a two-stage approach that first determines a sample's subtype using a recent module-driven approach, and secondly constructs a subtype-specific predictor to predict a metastasis event within five years. Our methodology is validated on a large compendium of microarray breast cancer datasets, including 43 replicate array pairs for assessing subtyping stability. Note that stratifying by subtype strongly reduces the training set sizes available to construct the individual predictors, which may decrease performance. Besides sample size, other factors like unequal class distributions and differences in the number of samples per subtype, easily obscure a fair comparison between subtype-specific predictors constructed on different subtypes, but also between subtype specific and subtype a-specific predictors. Therefore, we constructed a completely balanced experimental design, in which none of the above factors play a role and show that subtype-specific event predictors clearly outperform predictors that do not take subtype information into account.