Brain metastasis is common in patients with breast cancer, and leading to cognitive problems, poor quality of life, and rapid mortality. Despite the fact that brain metastases occur in 5 of breast cancer patients overall and 30 in patients with high expression of HER2, there are few treatment or prevention options. Integrins are a large family of cell surface proteins that are important for the internal structure of cells and also cell interactions with other cells and the biological microenvironment. We have evidences showing that the specific integrin protein v may be particularly important in cancer metastasis. First, breast cancer cell clones with high levels of v integrin migrate rapidly and infiltrate in rat brain, while clones with low v integrin do not, and v integrin interacts with HER2 to have the highest level of mobility and invasion. Second, decreasing v integrin also decreases the localization of HER2 in the cell membrane where it is active, and increases the amount of HER2 in lysosomes where it is broken down. Finally, we have new preliminary results showing that metastatic-prone alpha v-integrin positive of MDA-MB231BR clones are more resistant to chemo drugs than v-integrin negative cells with same genetic and molecular origin. Our results suggest that v integrin has a dual role in breast cancer brain metastasis, first to increase cancer cell binding and invasion into the brain, and second to provide the proper cellular location for HER2 activity.