Abstract: Although endocrine therapies, targeted therapies, and other methods are the main treatments for advanced estrogen receptor-positive breast cancer, the clinical treatment of endocrine resistance is more common. With the study of CDK4/6, the PI3K AKT1- mTOR signaling pathway, and other drug resistance mechanisms, targeted therapy for advanced estrogen receptor- positive breast cancer has become a popular research topic. Other treatments, such as gene therapy, may also provide new breakthroughs. How to choose the best treatment, best treatment time, and other issues for different patients remain as challenges for advanced estrogen receptor-positive breast cancer treatment.