The Biology of Breast Cancer in Brain Metastasis

Abstract : Breast cancer is the second most common cause of brain metastases; diagnosed in 10 to 15% of breast cancer patients and found at autopsy in 20 to 30%. Survival after detection of brain metastases can be short, and the therapy currently available only offers the hope of surviving one year to 20% of patients. Relatively little is known about how breast cancer cells metastasize to the brain, and what phenotypes characterize these cells. This is due in large part to the lack of suitable experimental models. The objective of the application is to develop experimental models to study the pathogenesis of breast cancer brain metastases, using intra-carotid artery injection of breast cancer cells into nude mice. This model will be used to test the hypothesis that brain metastases arise from the survival and growth of unique populations of cells. We found that a variant of the MDA-MB-23 1 breast cancer line, resulting from three cycles of injection and recovery of cells from brain metastases, has significantly greater potential for experimental metastasis in the brain of mice, following injection into the carotid artery. This variant will be used in continuing studies of the phenotype of breast cancer cells that metastasize to brain.