Mechanism of action

  • The growth of HR+ breast cancer is dependent on cyclin D1, a direct transcriptional target of the ER2,3

    • Cyclin D1 activates CDK4/6 resulting in G1–S phase transition and entry into the cell cycle2,3
    • Cell-line models of endocrine resistance remain dependent on cyclin D1 and CDK4/62,3
  • IBRANCE is an orally active selective inhibitor of CDK4 and CDK6 kinases4,5
  • IBRANCE blocks Rb phosphorylation at concentrations of 9–15 nmol/l, inducing G1 arrest in Rb+ tumour cell lines4
  • Synergy between ER and CDK4/6 has led to IBRANCE being developed in combination with endocrine therapy as treatment for HR+/HER2- mBC5

Adapted from Cadoo KA, et al. Breast Cancer Targets and Therapy. 2004;6:123–33. 

CDK, cyclin dependent kinase; AI, aromatase inhibitor; ER, endocrine receptor; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; LHRH, lutenising homone-releasing hormone; mBC, metastatic breast cancer; Rb, retinoblastoma protein. 


  1. IBRANCE® Summary of Product Characteristics.
  2. Thangavel C, et al. Endocr Relat Cancer. 2011;18:333–45. 
  3. Cadoo KA, et al Breast Cancer Targets and Therapy. 2014;6:123–33. 
  4. Fry DW, et al. Mol Cancer Ther. 2004;3:1427–38. 
  5. VanArsdale T, et al. Clin Cancer Res. 2015;21:2905–10.

PP-IBR-GBR-1932. December 2019