In recent years，the emergence of cyclin-dependent kinase 4/6 （CDK4/6） inhibitors has revolutionized the treatment of hormone receptor-positive （HR+） breast cancer. Currently，CDK4/6 inhibitors combined with endocrine therapy （ET） have become the standard first-line treatment for HR+/HER-2- advanced breast cancer，significantly extending progression-free survival （PFS）. However，during first-line treatment，there are some challenges regarding the timing of CDK4/6 inhibitors administration，combination drugs，eligible patient populations，and the application of liquid biopsy. The progression of disease and emergence of drug resistance following CDK4/6 inhibitor treatment have become clinical challenges. Assessing the sensitivity to endocrine therapy and the pattern of disease progression is crucial for determining subsequent treatment strategies for patients. For patients still dependent on endocrine therapy，priority should be given to genetic testing （ESR1，PAM pathway，BRCA mutation） to select targeted inhibitors combined with ET，or cross-line CDK4/6 inhibitors. For those unsuitable for ET，novel antibody-drug conjugates and chemotherapy are preferred options. With the development of more oral selective estrogen receptor down regulators，PI3K inhibitors and additional targets，precision-based individualized treatment will become the future trend.