New agents for endocrine resistance in breast cancer

Estrogen receptor positive (ER+) and HER2-negative (HER2-) breast cancer (BC) is the most common BC subtype, defined by expression of the ER and absence of HER2 amplification. Endocrine treatment (ET), aiming at therapeutic blockade of ER signaling, represents the therapeutic mainstay for patients with both early and advanced disease. Despite its wide therapeutic efficacy, ET fails for a proportion of ER+, HER2- BC patients with early disease who develop endocrine resistance, resulting in disease recurrence. Endocrine resistance occurs almost invariably in patients with metastatic disease. Recently, increasing understanding of the molecular mediators of endocrine resistance has been achieved. This review focuses on the molecular mechanisms mediating endocrine resistance, on molecularly targeted agents to overcome or delay it, and potential predictive biomarkers for accurate patient stratification.