Indeed, there is a strong rationale to evaluate CDK4 and 6 inhibitors in HR+/HER2+ BC, since CDK4 and 6 pathways have been reported to be involved in HER2-targeted therapy resistance, and the pharmacological inhibition of CDK4 and 6 was shown to restore cancer cell sensitivity to the HER2 blockade [18,27,114]. Here, CDK4 is linked to breast cancer.