Breast cancer is one of the most common tumors that present with brain metastasis, a late complication of progressive metastatic disease, for which effective treatment options are limited. Whether the energy metabolism of brain metastatic breast cancer cells also differ from the non-brain metastatic cancer cells is completely unclear. In our studies, we found that brain metastatic breast cancer cells can survival completely independent of glucose due to a significant up-regulation of the key gluconeogenic enzyme fructose-1 ,6-biphosphatase type 2 (FBP2). Inhibition of FBP2 can be used for treatment of breast cancer brain metastasis.