New Insights in Estrogen Receptor (ER) Biology and Implications for Treatment

Purpose of Review: Estrogen receptor-positive (ER+) breast cancer represents the majority of breast cancer diagnoses and is the leading cause of cancer death in women. Endocrine therapy is the principal treatment strategy for ER+ breast cancer. However, resistance to endocrine therapy, either de novo or acquired, is commonly observed, resulting in disease relapse and progression. This review will focus on recent progress in our understanding of ER biology and the implications for treatments. Recent Findings: Advances in genomic technology and laboratory investigations have led to the identification of somatic mutations, including treatment-emergent ESR1 mutations, and aberrant activation of growth factor receptor signaling pathways and cell cycle machinery that are associated with estrogen-independent proliferation and resistance to endocrine therapy. A plethora of molecularly targeted agents are being developed to overcome these resistance mechanisms, among which inhibitors against the mammalian target of rapamycin (mTOR) and cyclin-dependent kinases (CDK) 4/6 are now in clinical use. Summary: Advances in our understanding of ER biology have impacted the treatment landscape of ER+ breast cancer. Ongoing biomarker research on tumor specimens and cell-free tumor DNA will continue to generate important biological insight toward improving individualized treatment strategies for patients with ER+ breast cancer.