Notwithstanding these very promising results obtained in laboratory, when the activity of Palbociclib in combination with anti-estrogen therapy in patients with metastatic hormone receptor positive (HR+) breast cancer (BC) was firstly reported, it was unexpected and impressive, stimulating the rapid design and clinical development of other CDK4/6 inhibitors (CDK-i) (7–9). This evidence concerns the gene CDK4 and breast cancer.