Abstract:Luminal breast cancer (HR+/HER2- BRCA) is the most prevalent type of breast cancer, and endocrine therapy is an important means to prolong the overall survival of patients. However, the problems of endocrine therapy resistance and distant recurrence have not been effectively addressed. How to reduce, delay or even reverse the occurrence of endocrine therapy resistance is the focus of current research. Thanks to the continuous development of modern science and technology, significant progress has been made in the study of breast cancer drug resistance at the molecular and genetic levels, initially revealing the pathways of endocrine therapy resistance, such as gene mutation of estrogen receptor α, cell cycle protein-dependent kinase 4/6 inhibitor resistance pathway, histone deacetylase inhibitor resistance pathway, and so on, which have laid the foundation for promoting the development of precision therapy. In this paper, we summarized the mechanism of action of HR+/HER2- BRCA endocrine drug therapy, the mechanism of resistance generation and its research progress in clinical treatment, as well as the prospect of future research.