Chromatin landscape and endocrine response in breast cancer

Over two-thirds of breast cancers rely on estrogen receptor alpha (ER alpha) for their growth. Endocrine therapies antagonize estrogen-dependent ER alpha activation but resistance to these treatments occurs and is associated with poor prognosis. Crosstalk between alternative survival pathways and ER alpha are currently held as the primary cause of resistance. However, blocking these pathways does not cure endocrine therapy resistant breast cancer suggesting the existence of additional mechanisms. While cancer is commonly considered a genetic disease, the importance of epigenetic events in promoting tumor initiation and progression is increasingly recognized. Here, we consider how epigenetic modifications and alterations to the chromatin landscape contribute to endocrine therapy resistance by modulating ER alpha expression or altering its genomic activity.