emerging role of brain metastases in the prognosis of breast cancer patients

: Cancer starts with one rogue cell. Through mutations and genomic alterations, the cell acquires specific and stem cell-like characteristics necessary for invasion of a distant organ and ultimately metastasis. Metastatic brain cancer is a particularly formidable disease because of its poor prognosis and the highly resistant nature of the tumor to chemotherapy. Although several types of primary tumors have a tendency to metastasize to the brain, the incidence of brain metastases has increased dramatically in some subsets of breast cancer patients. Several conventional treatments are available, but success is limited and often short-lived. Given that no standard treatment options exist, there is a significant need to investigate the biology of these clinically recalcitrant tumors. this can trigger the production of iL-6 through activation of nuclear factor- κ B. 1 ( 1 ). Bradykinin, substance P, 5-HT (serotonin) and histamine acting on astrocytes can lead to the formation of ATP and PGs, with effects on vascular tone and endothelial permeability ( 2 ) by mechanisms that are known to involve endothelium. Lipopolysaccharide (LPS), formed in infections, leads to the release from microglia of TNF α , iL-1 β , and reactive oxygen species (including O 2 •- ), all of which have the ability to open the blood–brain barrier ( 3 ). Astrocytes downregulate tPA production via TGF β , but there is still sufficient tPA to open the blood–brain barrier, leading to an influx of tPA from the blood ( 4 ). Following disruption of the blood–brain barrier involving a decrease in agrin expression, K + and Glu from the blood can reach the brain extracellular space. AQP4 is upregulated on the astroglial endfeet, leading to astroglial swelling ( 5 ). Reprinted by permission from Macmillan Publishers Ltd: Nature Publishing Group 62 , copyright 2006.