CDK4 and breast cancer: In clinical studies, response to ICIs have best been seen in metastatic TN breast cancer which had a 19% response rate to pembrolizumab as a monotherapy.[16] In contrast, metastatic HR+ HER2 breast cancer either with pembrolizumab as a single agent (KEYN0TE-028) or in combination with a CDK4/6 inhibitor had an overall response rate of ~ 12%.[17, 18] In neoadjuvant therapy, pembrolizumab has improved pathologic complete response (pCR) in both HR + HER2- and TN.