This review examines the characteristics of the risk of disease recurrence in early-stage breast cancer, the evolution of the landscape of adjuvant endocrine therapies, the CDK4/6 inhibitor intensive adjuvant therapy population, a comprehensive comparison of the NATALEE and monarchE trials, the development of the future therapeutic landscape, the biomarkers and mechanisms of action, and a detailed account of the use of CDK4/6 inhibitors in early breast cancer. Here, CDK4 is linked to breast carcinoma.