On the other side, it has been demonstrated that the PAM50 molecular subtypes are prognostic in patients treated with CDK4/6 inhibitors16,18,19 and accumulated evidence suggests that the combination of endocrine therapy with palbociclib might be less effective than combination with ribociclib in patients with advanced HR+/HER2- and HER2-enriched breast cancer. The gene discussed is CDK4; the disease is breast cancer.