Cyclin dependent kinase 4/6 inhibitors in early breast cancer: what is the role of Ki-67?

Abstract

Hormone receptor-positive and HER2-negative early breast cancer accounts for approximately 70% of all breast cancer diagnoses. In this setting, adjuvant endocrine therapy significantly improves survival outcomes, with selective use of neoadjuvant or adjuvant chemotherapy, as guided by clinical, pathological, and molecular recurrence risk assessments. To our knowledge, the monarchE study is the first randomised, clinical, phase 3 trial to show benefit, in terms of invasive disease-free survival, from the addition of the cyclin dependent kinase 4/6 (CDK4/6) inhibitor abemaciclib to adjuvant endocrine therapy in patients with high-risk hormone receptor-positive, HER2-negative, and lymph node-positive early breast cancer. 1 Johnston SRD Harbeck N Hegg R et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 2020; 38: 3987-3998 Google Scholar , 2 Harbeck N Rastogi P Martin M et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021; 32: 1571-1581 Google Scholar These results led to the subsequent approval of abemaciclib by the US Food and Drug Administration (FDA) in October, 2021, restricted to patients who have tumours with immunohistochemical Ki-67 expression of 20% or higher, as measured by the companion diagnostic MIB-1 pharmDx assay (Dako Omnis, Agilent Technologies, Santa Clara, CA, USA).