CDK4 and breast cancer: Moreover, new small molecule protein kinase inhibitors (PKIs) have appeared, e.g. the cyclin-dependent kinase 4/6 inhibitors (CDKi), which are the first-line therapy for metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer and have recently been approved by the EMA as adjuvant therapy for early breast cancer at high risk of recurrence.3