An update on chemotherapy and tumor gene expression profiles in breast cancer

Various trials have attempted to develop gene expression profiles (GEPs) that may provide a better predictor of clinical outcome over traditional clinicopathological criteria.

The review focuses on two main areas: trials examining chemotherapy-induced GEP changes pre- and post-treatment, and studies correlating baseline signatures with chemosensitivity. In the first part of the article, the authors specifically cover areas pertaining to general/drug-specific tumor GEP changes and GEP changes between responders versus non-responders in specific molecular subclasses. The authors also discuss non-tumor-specific signatures, and provide a comparison of different biopsy methods. The authors also discuss the challenges that must be overcome in this area, looking at the clinical application of gene expression profiling and some of the multigene assays which have gained clinical utility.

Current studies are challenged by a number of issues including: small sample sizes, retrospective analyses, varying chemotherapy regimens and response end points, the need for fresh frozen samples, distinct gene signatures in multiple platforms with minimal overlap and inherent microarray technological complexities. To date, no pharmacogenomic drug-specific predictor has been implemented clinically. Future studies should focus on distinct molecular subgroups by pooling resources and validation in well-powered randomized trials. Incorporating GEPs with newer biotechnological modalities may provide a more robust predictive model.