Smid et al. highlight the penetrance of brain metastasis in HER2 + and TNBC disease [35], which is supported by data from Hicks et al. which implicates the propagation of CNS metastases to occur in the setting of ER negative, basal cytokeratin 5/6 expressing cancers, or in those overexpressing HER2/ErbB receptor tyrosine kinase [36]. This evidence concerns the gene ESR1 and cancer.