The TROPiCS-02 phase III trial recruited ER+/HER2− breast cancer patients progressing after three different lines of systemic therapy, a CDK4/6i among them; in this setting, a significant prolonging of PFS to 5.5 months occurred with sacituzumab govitecan, versus 4 months with the physician’s choice chemotherapy; the clinical benefit was independent of Trop-2 expression. This evidence concerns the gene CDK4 and breast carcinoma.