Advances in Endocrine Resistance and Targeted Therapy of Advanced Hormone Receptor-Positive Breast Cancer

Hormone receptor(HR)-positive breast cancer accounts for approximately 70% of all breast cancer cases. Endocrine therapy benefits the majority of patients, but still, 20% to 40% of patients may experience resistance to endocrine treatment, leading to recurrence and progression of the disease. The efficacy of endocrine therapy in advanced HR-positive breast cancer can be influenced by genetic mutation, molecular pathways such as PI3K-AKT-mTOR, abnormal activation of cell cycle signaling, epigenetic modification, and the tumor microenvironment. Since the introduction of mTOR inhibitors represented by everolimus in 2012, there have been significant advancements in the research of endocrine-targeted therapies. The emergence of such drugs as antibody-drug conjugates and cyclin-dependent kinase 4/6 inhibitors has changed the treatment landscape for advanced HR-positive breast cancer patients, significantly improving patients' prognosis. This article reviews the mechanisms of resistance to endocrine therapy in advanced HR-positive breast cancer and the research progress in endocrine-targeted molecular therapies, in the hope of providing new perspectives on the future treatment of advanced HR-positive breast cancer.