Dysregulation of the cell cycle, especially in the cyclin D-cyclin dependent kinase (CDK) pathway, is a key component of carcinogenesis, also in breast cancer. Cyclin dependent kinase inhibition has emerged as an attractive targeted cancer therapy. Recently, three oral agents selectively targeting CDK 4/6 have been developed for the treatment of breast cancer: palbociclib (PD 0332991), ribociclib (LEE011), and abemaciclib (LY2835219). Clinical trials have shown an improvement in progression-free survival when palbociclib and ribociclib are used in combination with endocrine therapy. The next wave of studies will examine the efficacy of CDK 4/6 inhibitors in combination with other targeted therapies, in the (neo)-adjuvant situation, and in other breast cancer subtypes, such as HER2 positive breast cancer. Palbociclib and ribociclib recently received accelerated Food and Drug Administration approval for the treatment of hormone receptor positive advanced breast cancer in combination with endocrine therapy. This combination has become the new standard of care for the treatment of patients with hormone receptor positive breast cancer.

(BELG J MED ONCOL 2017;11(5):234–241)