Together, these data support distinctive roles for individual cell cycle checkpoint kinases in metastatic progression of breast cancer, with dysregulation of ATM associating with primary ER+/HER2− disease, CHEK2 with metastatic ER+/HER2− breast cancer, and ATR with metastatic disease that is ER agnostic but reliant on TP53 mutation. Here, TP53 is linked to breast carcinoma.