Embodiments of the present invention concern methods related to treating, prognosticating, and/or diagnosing at least brain metastatic breast cancer. Embodiments of the methods include characterizing circulating tumor cells for the presence or absence of EpCAM and, upon identification of EpCAM negative cells and identification of the status of other markers (such as heparanase and/or Notchl, for example), treating the individual based on the determination of the characterization.