Endocrine resistance and epigenetic reprogramming in estrogen receptor positive breast cancer

Despite the enormous advances during the last three decades, breast cancer continues to be the most frequent type of cancer as well as one of the most frequent cancer-related causes of death in women. Therapeutic management of patients with hormone receptor-positive breast cancer becomes very often a challenge, since de novo or acquired resistance deprives a significant percentage of the patients from the clinical benefit of the well-tolerated hormone therapy. Several molecular mechanisms are implicated in resistance to endocrine therapy, including changes in hormone receptor signaling, activation of parallel signaling pathways, modifications of cell cycle regulators, activation of different transcription factors as well as changes in stem cells activity. In addition, a growing number of studies supports the pivotal role of epigenetic changes not only in the initiation and progression of breast cancer, but also in resistance to endocrine therapy. These changes refer to DNA methylation, histone post-translational modifications as well as to ncRNAs alterations. In this review, we provide an overview of epigenetic mechanisms underlying the endocrine resistance focusing exclusively on breast cancer patients.