ESR1 and neoplasm: Cyclin-dependent kinases (CDKs) regulate cell cycle progression, and CDK4 and CDK6 induce hyperphosphorylation of the retinoblastoma protein, causing the progression of tumor cells from the G1 checkpoint to the S phase of the cell cycle.8,9,10 The development of endocrine resistance in breast cancer is associated with the deregulation of the cyclin D/CDK4-6/retinoblastoma pathway.11,12 Cyclin D is also a key target for estrogen-induced cell proliferation through the estrogen receptor.