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. Here, CDK4 is linked to breast cancer.