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

描述（由申请人提供）： 目前，乳腺癌的化学预防使用的策略来自成功的治疗，其中治疗相关的发病率阈值较高。许多妇女患乳腺癌的风险增加，但目前没有癌症，发现类似的发病风险不可接受，她们选择单独监测。在这一健康人群中，需要替代策略进行乳腺癌的化学预防。亚麻籽是一种天然食物来源，含有木酚素，植物雌激素和α-亚麻酸，ω-3脂肪酸。在临床前和临床研究中，亚麻籽消费已被报道通过抗雌激素活性和雌激素非依赖性机制在雌激素受体（ER）阳性和ER阴性乳腺癌中减少肿瘤生长，亚麻籽没有已知的严重副作用。一项试点研究提出了测试的中心假设，亚麻籽将是一个安全，有效的化学预防剂在健康的绝经前妇女在乳腺癌的高风险。中心假设将通过以下具体目标进行检验：确定每天摄入25克磨碎的亚麻籽1）是否会改变表达Ki-67和caspase-3的乳腺上皮细胞的比例（细胞凋亡的测量）六个月后在随机乳晕周围细针穿刺（RPFNA）样本;（2）RPFNA中雌激素调节基因cyclin D1、survivin和VEGF的改变; 3）在六个月后改变IGF-1和IGFBP-3的血清水平，和4）在绝经前妇女中产生任何显著的副作用，所述绝经前妇女基于升高的Gail和Claus评分而处于发生乳腺癌的增加的风险中，手术活检有乳腺癌史或单侧乳腺癌史，随机乳晕周围细针穿刺样本（RPFNA）Ki-67标记指数>1.5%。50名研究参与者将随机接受每天25克亚麻籽或6个月不干预。将记录合规性和影响亚麻籽验收的因素。乳腺癌风险的中间生物标志物将用作替代终点。生物标志物将包括Ki- 67标记指数和RPFNA的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。如果这项在高风险女性中进行的试点研究表明亚麻籽对乳腺癌风险的生物标志物有积极影响，并且被参与者接受，那么将提出一项更大的随机试验来评估亚麻籽对乳腺癌化学预防的影响。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，具有许多健康益处和很少的副作用。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年轻女性乳腺中生长细胞的数量，这些女性患乳腺癌的风险增加。

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.