Clinical implications of chemotherapy-induced tumor gene expression in human breast cancers.

IMPORTANCE OF THE FIELD: There has been much interest in generating gene signatures to predict treatment response in breast cancer. AREAS COVERED IN THIS REVIEW: There are at least 15 published studies that describe baseline tumor gene signatures predicting chemotherapy sensitivity. As an extension of these baseline studies, there have been at least 8 published studies evaluating chemotherapy-induced tumor genomic changes over time in human breast cancers. WHAT THE READER WILL GAIN: Studies on chemotherapy-induced gene expression changes were reviewed in detail. Drug-induced biological changes within the tumor shed light on mechanisms of drug resistance and provided valuable insights regarding genes and pathways that were regulated by different drugs, including therapeutic targets that could be exploited to overcome resistance. One study also suggested post-chemotherapy gene signatures to be more predictive of response and survival than the unchallenged baseline signatures. TAKE HOME MESSAGE: Studies on chemotherapy-induced changes, although informative, are logistically demanding to execute, often with significant attrition of collected samples resulting in small datasets. They are further limited by heterogeneity of study population, chemotherapy regimens used, timing of the post-therapy sample and definition of response endpoint, making cross-comparisons of studies and data interpretation difficult. Future studies should address these limitations, and should involve larger sample sets and prospective studies for validation.