Predicting resistance to endocrine therapy in breast cancer: It's time for epigenetic biomarkers (Review).

Notwithstanding the marked progress in breast cancer (BC) management, it still constitutes the most common malignancy in women and a major cause of morbidity and mortality, thus remaining a major health issue worldwide. Most BC cases are hormone receptor (HR) positive (luminal A or B molecular subtypes) and endocrine treatment (ET) is an important therapeutic modality at all disease stages. Nevertheless, despite substantial improvements in BC patient outcome, effectiveness of ET is limited, as up to 40% of patients eventually relapse or progress and endocrine resistant BC has a less favorable prognosis and constitutes a therapeutic challenge. The biological mechanisms underlying endocrine resistance are, however, still poorly understood. In this review, we focused on data regarding the main epigenetic mechanisms associated with the development of endocrine treated‑resistant BC described so far, including alterations in DNA methylation, non‑coding RNAs, chromatin remodeling, post‑translational histone modifications and histone variants. Notably, specific epigenetic alterations have been characterized in this subset of breast tumors and may be of clinical value for individualized patient management in the future.