A study evaluating the effect of flaxseed on biomarkers of breast cancer risk

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DESCRIPTION (provided by applicant): At present, breast cancer chemoprevention uses strategies derived from treatment successes where the threshold for treatment-related morbidities is higher. Many women who are at increased risk of developing breast cancer, but are currently cancer-free, find similar risks of morbidities unacceptable and they opt for surveillance alone. Alternative strategies are needed for chemoprevention of breast cancer in this healthy population. Flaxseed is a natural food source containing lignan, a phytoestrogen, and alpha-linolenic acid, an omega-3 fatty acid. Flaxseed consumption has been reported in preclinical and clinical studies to decrease tumor growth through anti-estrogenic activity and estrogen-independent mechanisms in both estrogen receptor (ER) positive and ER negative breast cancers, and flaxseed has no known serious side effects. A pilot study is proposed to test the central hypothesis that flaxseed will be a safe and effective chemopreventive agent in healthy premenopausal women at high risk of breast cancer. The central hypothesis will be tested with the following specific aims: determine if the daily consumption of 25 grams of ground flaxseed 1) alters the proportion of breast epithelial cells expressing Ki-67 and caspase-3 (a measure of apoptosis) after six months in random periareolar fine needle aspiration (RPFNA) samples; 2)alters estrogen regulated genes, cyclin D1, survivin and vascular endothelial growth factor (VEGF) in RPFNA samples ; 3) alters serum levels of IGF-1 and IGFBP-3 after six months and 4) produces any significant side effects in premenopausal women who are at increased risk of developing of breast cancer based on elevated Gail and Claus scores, history of atypia on surgical biopsy ,or history of unilateral breast cancer, and Ki-67 labeling index >1.5% on random periareolar fine needle aspiration samples (RPFNA). Fifty research participants will be randomized to receive either 25 grams of ground flaxseed daily or no intervention for 6 months. Compliance and factors that influence acceptance of flaxseed will be recorded. Intermediate biomarkers of breast cancer risk will be used as surrogate endpoints. Biomarkers will include Ki- 67 labeling index and caspase-3 of RPFNA, estrogen regulated genes, and serum levels insulin growth factor (IGF)-1 and insulin growth factor binding protein (IGFBP)-3. If this pilot study in high-risk women demonstrates that flaxseed favorably affects biomarkers of breast cancer risk and is accepted by participants, a larger, randomized trial will be proposed to evaluate ground flaxseed consumption for breast cancer chemoprevention. PUBLIC HEALTH RELEVANCE: New agents are needed to prevent breast cancer in young women. Flaxseed is a natural food with many health benefits and few side effects. It contains substances that may prevent breast cancer by decreasing the number of cells that are growing in the breast. This study will determine if flaxseed can reduce the number of growing cells in the breast of young women who are at increased risk of developing breast cancer.