Tumor-associated macrophages increase COX-2 expression promoting endocrine resistance in breast cancer via the PI3K/Akt/mTOR pathway.

Breast cancer is the most common malignancy in females. The emergence of endocrine resistance is frustrating for estrogen receptor (ER)-positive breast cancer patients even the efficacy of endocrine therapy is acceptable. Our previous study has shown that tumor-associated macrophages (TAMs) are associated with endocrine resistance, yet the mechanism remains unclear. This article is dedicated to discuss the role of TAMs in the endocrine resistance of breast cancer. It was found that tamoxifen-resistant MCF-7 cells induced more macrophages polarized into TAMs. Conversely, TAMs increased the expression of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2), which promoted tamoxifen resistance through the activation of the PI3K/Akt/mTOR signaling pathway in MCF-7 cells. Furthermore, clinical analysis supported that five-year progression-free survival (PFS) of breast cancer patients with abundant COX-2 expression in TAMs was shorter (p<0.05). Therefore, these results show a positive feedback loop between TAMs and breast cancer cells, suggesting that TAMs and COX-2 may be new therapeutic targets for breast cancer patients suffering from endocrine resistance.