Is there a role for continuation of CDK4/6 inhibition after progression on a prior CDK4/6 inhibitor in HR+/HER2− metastatic breast cancer?

Cyclin-dependent kinase 4 (CDK4) and CDK6 interact with cyclin D1 to hyperphosphorylate the retinoblastoma (RB1) gene product pRb early in the G1 phase of the cell cycle. This results in pRb inactivation and release of transcription factors that allow progression to the S phase.1 Cyclin D1 and CDK4 play particularly important roles in mammary gland biology and breast cancer2 and numerous molecular features suggest that the cyclin D–CDK4/6 pathway can be hyperactivated in human hormone receptor (HR)-positive breast cancers.