NATALEE (Slamon et al., 2024) and MonarchE (Johnston et al., 2023) trails found survival benefits of CDK4/6 inhibitors combined with endocrine therapy in HR-positive early breast cancer, whereas the results of the other two studies (Gnant et al., 2022; Loibl et al., 2021) indicated that CDK4/6 inhibitors did not improve survival outcomes in these patients. This evidence concerns the gene CDK4 and breast cancer.