The objective is to perform a proof of principle study in women at high risk for development of breast cancer, evaluating the effects of a natural lignan found in high levels in flaxseed. The source of lignan will be the commercial product Brevail (200 mg) which consistently provides the 50 mg of secoisolariciresinol diglycoside (SDG) and resultant serum enterolactone levels associated with reduction in breast cancer risk in epidemiologic studies. We will evaluate several biomarkers associated with increased risk for breast cancer including proliferation in hyperplastic ductal epithelium obtained by random periareolar fine needle aspiration (FNA), mammographic breast density, serum levels of insulin-like growth factor I (IGF-1) and its binding protein IGFBP-3, at baseline and after 12 months of Brevail. Change in these risk biomarkers will be correlated with change in serum enterolactone and enterodiol levels. It is anticipated that 50 pre-menopausal women with an adequate yield of cells on FNA and having at least 2% of cells that stain positive for Ki-67 will be enrolled in this pilot study.
Study aims to be investigated include estimation of: 1) change in proportion of benign epithelial cells expressing the proliferation antigen Ki-67; 2) change in mammographic density; 3) change in serum IGF-1/IGFBP-3; and 4) measurement of serum SDG, enterolactone, and enterodiol levels and correlation with modulation of risk biomarkers. This study will provide an estimate of the magnitude of change over 12 months for these risk biomarkers, which will provide a basis for sample size calculation for a larger placebo controlled randomized trial in the future. This study will provide preliminary evidence as to whether premenopausal women at high risk for breast cancer are likely to benefit from lignans if serum enterolactone levels are maintained above 34 nM. If positive, the results of this study will be critical to the design and implementation of a placebo-controlled Phase II prevention trial with Brevail and/or commercial flaxseed. ? ?
|Fabian, Carol J; Kimler, Bruce F; Zalles, Carola M et al. (2010) Reduction in Ki-67 in benign breast tissue of high-risk women with the lignan secoisolariciresinol diglycoside. Cancer Prev Res (Phila) 3:1342-50|