The targeted treatment options for patients with HER2-low BC will either end upon failure of sequenced endocrine therapies (ET; tamoxifen, aromatase inhibitors or fulvestrant with or without cyclin-dependent kinase 4 and 6 inhibitors or everolimus or alpelisib), in case of HR positivity or are restricted to a subset of those with HR negativity (namely immunotherapy for patients whose tumors are positive for programmed death-ligand 1 (PD-L1) receptor expression or poly(ADP-ribose) polymerase inhibitors for those with germline BRCA mutations) [11,12]. The gene discussed is CDK4; the disease is breast cancer.