A systematic search was conducted in PubMed, Embase, and ClinicalTrials.gov from 1 July 2004, to 30 August 2025, to identify relevant clinical trials addressing post-CDK4/6 inhibitor treatments in patients with hormone receptor positive (HR+) and human epidermal growth factor receptor 2-negative (HER−) advanced breast cancer. The gene discussed is CDK4; the disease is breast cancer.