Cyclin-Dependent Kinase 4/6 Inhibitors in Neoadjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer

The landscape of therapeutic options for the treatment of hormone receptor (HR)-positive (HR+) HER2(-) breast cancer (BC) has been profoundly changed by the introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors into the metastatic setting. Currently all CDK4/6 inhibitors are approved only in the metastatic setting by Food and Drug Administration (FDA) and European Medicine Agency (EMA), whereas their role in the neoadjuvant setting is still at an investigational stage. Exploitation of novel agents such as CDK4/6 inhibitors to improve the efficacy of neoadjuvant endocrine therapy (ET) or to overcome de novo resistance to ET is an area of research under active evaluation. We present a review of the currently available data and ongoing clinical trials that are evaluating the role of CDK4/6 inhibitors in neoadjuvant therapy of HR+ HER2(-) early BC, and also illustrate translational aspects, such as the potential biomarkers of response to these new therapeutic agents.