Abstract 185: Secoisolariciresinol diglucoside (SDG, flaxseed lignan) improves biomarkers of early mammary gland cancer progression in a rat model of breast and ovarian cancer.

Abstract

Abstract Breast cancer prevention efforts increasingly are focused on potentially beneficial dietary modifications due to their ease of implementation, wide acceptance and excellent subject compliance. SDG is a bioactive component of flaxseed suggested to have beneficial SERM-like effects in females at high risk for the development of breast cancer. In parallel with a human phase II prevention trial, female Sprague Dawley rats (n=10-12/group) received 0, 1, 10 or 20 mg/kg/day SDG in the feed. Simultaneously, rats were induced to concurrent mammary and ovarian cancer progression in a previously validated model using sustained release 17β-estradiol and local ovarian DMBA treatment starting at 6 weeks of age. Serum was collected at 3 weeks to measure steady state SDG metabolite concentrations. Mammary gland and ovarian tissues were collected at 3 months post-treatment and examined for changes in epithelial cell proliferation (Ki-67, cell counts), histopathology and dysplasia scores as well as a panel of cancer risk and progression biomarker genes. Carcinogen treatment markedly elevated dysplasia scores while SDG decreased dysplasia in a dose-dependent fashion, with an approximately 50% improvement the highest dose. Mammary epithelial cell numbers were increased by carcinogen and this effect was mitigated similarly at all doses of SDG and reflected in reduced Ki-67 expression. Overall, SDG decreased mammary epithelial proliferation and dysplasia resulting from carcinogen treatment. This preclinical benefit occurred at serum concentrations similar to our human pilot study, in which dietary SDG reduced KI-67 expression in mammary epithelial cells, and decreased the proportion of women with RPFNA atypia. Supported in part by funds from Komen for the Cure grant KG101039. Citation Format: Devora Delman, Bruce F. Kimler, Carol J. Fabian, Brian K. Petroff. Secoisolariciresinol diglucoside (SDG, flaxseed lignan) improves biomarkers of early mammary gland cancer progression in a rat model of breast and ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 185. doi:10.1158/1538-7445.AM2013-185