Abstract CN04-01: New drugs for the chemoprevention of experimental breast cancer

Tamoxifen, raloxifene and exemestane are all effective for prevention of estrogen-receptor positive (ER+) breast cancer in women. Despite these significant advances, novel drugs are needed for the chemoprevention of estrogen-receptor negative (ER−) breast cancer, especially for women with hereditary breast cancers who frequently harbor BRCA (breast cancer-associated gene) mutations. Currently, “watchful waiting” or bilateral prophylactic mastectomy is offered to these patients, although these high risk women are ideal candidates for an effective, safe chemopreventive regimen. Two relevant mouse models were used to study drugs that are used to treat human breast cancer or drugs with known chemopreventive activity in other animal models. When conditional knockout (co) of BRCA1 is coupled with a mutation in p53, Brca1Co/Co;MMTV-Cre;p53+/− mice develop ER− mammary tumors within 6–10 months of age. In the PyMT mouse model, the polyomamiddle T oncoprotein drives carcinogenesis by inducing significant infiltration of tumor-associated macrophages (TAM). The efficacy of synthetic triterpenoids, rexinoids, histone deacetylase inhibitors, and PARP (Poly ADP ribose polymerase) inhibitors as well as potential biomarkers and mechanisms for these drugs will be discussed. Supported by the Breast Cancer Research Foundation and Komen for the Cure Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN04-01.