Abstract: A new target in cancer treatment involves tumor-associated macrophages(TAMs) which are infiltrated in microenvironment.By secreting a wide range of cancer-promoting cytokines, such as vascular endothelial growth factor, interleukins, and matrix metalloproteinase, TAMs can promote the proliferation, invasion, and metastasis of cancer cells.Cyclooxygenase-2(COX-2), an inflammatory factor that is significant for angiogenesis and immunoregulation within the local microenvironment, may also contribute to cancer progression and act as a novel target for breast cancer therapy.Several COX-2 inhibitors, such as celecoxib, have shown potential as suppressors of TAMs and the microenvironment.Hence, the current study discusses the crosstalk between TAMs-delivered important cytokines and COX-2 in the breast cancer microenvironment, and then analyzes the value of homologous antagonists alone or in combination with COX-2 inhibitors.This paper aims to provide the theoretical principle of multi-target selection in TAMs blockage, and offer a new direction for biological targeted therapy in breast cancer treatment.