Abstract A103: The synthetic triterpenoid CDDO-methyl ester targets tumor-associated macrophages to delay carcinogenesis in the PyMT model of estrogen receptor negative breast cancer

Breast cancer is the most common cancer among women in the United States. The incidence rates of breast cancer are no longer significantly declining, and approximately 40,000 women die from the disease each year. Hence, novel drugs are needed for the prevention and treatment of the disease. Synthetic triterpenoids are a promising new class of compounds with chemopreventive activity in a variety of preclinical cancer models. We tested the methyl ester derivative of the synthetic triterpenoid, 2-cyano-3, 12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me), in a relevant model of ER-negative breast cancer. In this mouse model, the polyoma-middle T (PyMT) oncoprotein drives carcinogenesis in the mammary gland. The developing tumors recapitulate key features of the human disease including significant infiltration of tumor-associated macrophages (TAM). Depletion of TAMs has been previously shown to delay tumor progression. PyMT mice were fed CDDO-Me (50 mg/kg diet), starting at 4 weeks of age. CDDO-Me significantly increased the age of mice at onset of first tumor by an average of 4.3 weeks (P Citation Information: Cancer Prev Res 2011;4(10 Suppl):A103.