In HR-positive disease, a main direction of research has been the development of multi-class regimens to inhibit secondary processes, such as treatment resistance (mTOR/PI3K-inhibitors; insulin growth factor receptor [IGF(R)]-inhibitors; epidermal growth factor receptor [EGFR]-inhibitors; fibroblast growth factor receptor [FGFR]-inhibitors), cell cycle regulation (CDK4/6-inhibitors) or effects of the tumor micro-environment (bisphosphonates). Here, CDK4 is linked to neoplasm.