Epigenetic reprogramming in breast cancer: from new targets to new therapies

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death among women in the United States. Recently, interest has grown in the role of epigenetics in breast cancer development and progression. Epigenetic changes such as DNA methylation, histone modifications, and abnormal expression of non-coding RNAs emerged as novel biomarkers in breast cancer diagnosis, therapy, and prevention. This review focuses on the most recent mechanistic findings underlying epigenetic changes in breast cancer development and their role as predictors of breast cancer risk. The rapid progress in our understanding of epigenetic findings in breast cancer has opened new avenues for potential therapeutic approaches via identification of epigenetic targets. We highlight the development of novel epigenetically targeted drugs, relevant clinical trials in breast cancer patients, and recent approaches combining epigenetic agents with chemotherapy and/or endocrine therapy that may incrementally improve long-term outcomes in appropriately selected breast cancer patients. Biomarkers of response are needed, however, to identify patient subsets that are most likely to benefit from epigenetic treatment strategies.