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

描述(由申请人提供)： 目前，乳腺癌化学预防使用的策略来自治疗成功，其中与治疗相关的发病率的门槛较高。许多女性患乳腺癌的风险增加，但目前没有癌症，她们认为类似的患病风险是不可接受的，她们选择单独进行监测。在这个健康的人群中，需要有替代的策略来化学预防乳腺癌。亚麻籽是一种天然的食物来源，含有木脂素(一种植物雌激素)和α-亚麻酸(一种omega-3脂肪酸)。临床前和临床研究表明，在雌激素受体(ER)阳性和ER阴性的乳腺癌中，亚麻籽的摄入通过抗雌激素活性和雌激素非依赖性机制来抑制肿瘤生长，亚麻籽没有已知的严重副作用。有人提议进行一项初步研究，以检验中心假设，即亚麻籽将是一种安全有效的化学预防药物，适用于患有乳腺癌的健康绝经前妇女。中心假设将以以下具体目标进行检验：1)确定每天食用25克磨碎的亚麻籽是否会改变随机乳晕周围细针抽吸(RPFNA)样本中6个月后表达Ki-67和caspase-3(衡量细胞凋亡的指标)的乳腺上皮细胞的比例；2)改变RPFNA样本中的雌激素调节基因、细胞周期蛋白D1、Survivin和血管内皮生长因子(VEGF)；3)6个月后血清IGF-1和IGFBP-3水平的变化；4)根据Gail和Claus评分升高、手术活检异型性病史或单侧乳腺癌病史以及随机乳晕周围细针吸取标本(RPFNA)的Ki-67标记指数&Gt；1.5%，对绝经前乳腺癌高危女性产生任何显著的副作用。50名研究参与者将被随机分成两组，一组每天服用25克磨碎的亚麻籽，另一组在6个月内不进行干预。将记录亚麻籽的合规性和影响接受的因素。乳腺癌风险的中间生物标志物将被用作替代终点。生物标志物将包括RPFNA的Ki-67标记指数和caspase-3，雌激素调节基因，以及血清胰岛素生长因子(IGF)-1和胰岛素生长因子结合蛋白(IGFBP)-3水平。如果这项针对高危女性的初步研究表明，亚麻籽有利于影响乳腺癌风险的生物标记物，并被参与者接受，将提出一项更大规模的随机试验，以评估磨碎的亚麻籽对乳腺癌化学预防的作用。公共卫生相关性：需要新的药物来预防年轻女性的乳腺癌。亚麻籽是一种天然食品，对健康有许多好处，副作用很少。它含有的物质可以通过减少乳房中生长的细胞数量来预防乳腺癌。这项研究将确定亚麻籽是否可以减少患乳腺癌风险增加的年轻女性乳房中生长的细胞数量。

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.