CDK4 and breast carcinoma: High TIS scores, mutations in TP53, and features of HRD are common characteristics of more aggressive luminal breast cancer phenotypes as well as basal-like/triple negative breast cancers (37), suggesting that endocrine-based therapies and CDK4/6 inhibition may not be adequate and that other targeted therapies, such as PARP inhibitors or immmunotherapies might be better matched to these tumor biologies despite their positive HR status.