Metastasis is the primary cause of death from breast cancer, invasive carcinoma cells in mouse and rat mammary tumors co-migrate accompanied by macrophages towards intravasation sites . The intravasation occurs at sites where a TIE2-expressing macrophage, a mena-expressing tumor cell, and an endothelial cell are in direct contact, forming a micro-anatomic structure called tumor micro-environment of metastasis (TMEM). Ablation of the presence or activity of the TMEM associated macrophages blocks intravasation at TMEM demonstrating an essential role of perivascular macrophages in TMEM function. Rebastinib, a TIE2 inhibitor , blocks TMEM assembly and function in-vivo and in-vitro assays. We hypothesize that rebastinib combined with antitubulin therapy (eribulin or paclitaxel) could improve clinical outcomes in breast cancer by preventing intravasation at TMEM sites and preventing further metastasis.