Abstract
Estrogen affects cyclin signaling which results in proliferation of breast cancer cells. Breast cancers expressing hormone receptors (known as hormone receptor-positive or HR+ breast cancers) are characterized by dysregulation of cyclin-dependent kinase 4 and 6 (CDK4/6) activity due to overexpression and amplification of genes associated with the cell cycle. Inhibition of CDK4/6, in combination with endocrine therapy (ET), have shown significant clinical efficacy in treating HR+, human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer, leading to global approval of this combination. Abemaciclib is a CDK4/6 inhibitor with higher potency and inhibits a wider range of CDKs compared with other CDK4/6 inhibitors. The MonarchE study is a global, open-label, randomized phase III study of the efficacy of 2-year abemaciclib treatment, together with standard adjuvant ET, in patients who underwent surgery for early-stage HR+, HER2- breast cancer with anatomical or pathological high-risk recurrence features. Preplanned interim analysis of the MonarchE study showed significantly improved invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) with the use of abemaciclib-ET combination therapy in comparison with ET alone. This review focuses on the emerging results and limitations of the MonarchE study in determining the way forward from the CDK4/6-ET combination treatment in HR+, HER2- early-stage breast cancer.