Cyclin-dependent kinase (CDK4/6) inhibitors in combination with endocrine therapy are currently the optimal first line treatment for hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) non-amplified metastatic breast cancer (MBC). However, not all patients benefit from this treatment and all patients will inevitably progress. Identifying therapeutic strategies in this setting is therefore of immediate clinical importance. We present an overview of the mechanisms of resistance to CDK4/6 inhibitors and review potential biomarkers that may guide therapy selection. We also discuss the use of CDK4/6 inhibitors in the context of non-HR-positive/HER2-non-amplified breast cancer and in combination with therapies other than endocrine therapy.
Breast Neoplasms/genetics , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Cyclin-Dependent Kinase 4/therapeutic use , Cyclin-Dependent Kinase 6/antagonists & inhibitors , Cyclin-Dependent Kinase 6/therapeutic use , Receptor, ErbB-2/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cyclin-Dependent Kinase 4/pharmacology , Cyclin-Dependent Kinase 6/pharmacology , Female , Humans , Protein Kinase Inhibitors/therapeutic use
