DNA methylation markers - an opportunity to further individualize therapy in breast cancer?

Abstract

Over the last few decades, a wealth of treatment options have become available for breast cancer. To specifically direct those therapies to patients with the highest need who will receive the greatest benefit, biomarkers are urgently needed. Two specific needs seem to be most pressing: first is the need for prognostic markers, which would determine which group of patients may recover without adjuvant chemotherapy. Second, predictive markers for specific treatments, such as different endocrine treatments, chemotherapies or targeted drugs, are expected to play a major role in the near future. Ideally, such markers should be strong single markers, or low-complexity marker panels containing only a few markers, to allow for easier assay development and improved reproducibility. The possibility to measure the marker(s) in formalin-fixed specimens would greatly facilitate integration into routine clinical practice. A common and early event in breast cancer is aberrant DNA methylation within gene regulatory regions, affecting a variety of genes with different functions. Data from recently published studies indicate that altered DNA methylation carries prognostic as well as predictive information in breast cancer. Together with the technical advantages of a DNA-based marker, DNA methylation may well constitute the ideal biomarker to further individualize breast cancer treatment. Here the recent literature is reviewed and the most interesting markers, which have the potential to significantly change breast cancer treatment and, therefore, warrant further systematic clinical validation, are highlighted.