CDK4 and metastatic neoplasm: In metastatic disease, the CDK4/6 inhibitors associated with endocrine therapy radically changed clinical practice due to a remarkable improvement in terms of PFS compared to hormone therapy alone of 9–13 months in first line [9,10,15,16,24,25], of 8–11 months in both first second line [26,27,28,29]), and of 5–7 months in second line [11,12,13,22,23].