Breast cancer brain metastasis: molecular mechanisms and directions for treatment

The development of brain metastasis (BM) of breast cancer is usually a late event with deleterious effect on the prognosis. Treatment options for intracerebral seeding of breast cancer are limited and, so far, nonspecific. Molecular detailing of subsequent events of penetration, seeding, and outgrowth in brain is highly relevant for developing therapeutic strategies to treat, or prevent, BM. We scrutinize recent literature for molecules and pathways that are operative in the formation of breast cancer BM. We also summarize current data on therapeutic efforts to specifically address BM of breast cancer. Data on molecular pathways underlying the formation of BM of breast cancer are sketchy and to some extent inconsistent. The molecular makeup of BM differs from that of the primary tumors, as well as from metastases at other sites. Current efforts to treat breast cancer BM are limited, and drugs used have proven effects on the primary tumors but lack specificity for the intracerebral tumors. More basic research is necessary to better characterize BM of breast cancer. Apart from the identification of drug targets defined by the intracerebral tumors, also targets in the molecular pathways involved in passing the blood-brain barrier and intracerebral tumor cell growth should be revealed.