In detail, the combination of endocrine therapy (ET) plus cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), palbociclib, ribociclib and abemaciclib, represents the mainstay of treatment for patients with HR+/HER2- metastatic disease, while for triple negative tumors, chemotherapy is still the standard of care, although promising drugs are emerging as novel therapeutic weapons. This evidence concerns the gene CDK4 and metastatic neoplasm.