TP53 and cancer: First, the presence of TP53 mutations in the great majority of CNS metastatic lesions implies that therapeutic strategies aimed at exploiting loss of p53 function could be highly effective in brain metastasis, even if the primary breast cancer is wild type for TP53. Second, the results raise the possibility that patients at high risk for intra-cranial metastasis might be identifiable from detection of TP53 mutations in the primary cancer and interventions such as prophylactic cranial irradiation considered.