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

一项评估亚麻籽对乳腺癌风险生物标志物影响的研究

• 批准号: 7472138
• 负责人: Swati Kulkarni
• 金额: $ 20.95万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7472138
• 关键词: Adverse effects; Affect; Apoptosis; Apoptotic; Atypia; Binding Proteins; Biological Markers; Biopsy; Breast; Breast Cancer Prevention; Breast Cancer Treatment; Carcinoma; Cell Count; Cells; Characteristics; Chemoprevention; Chemopreventive Agent; Clinical Research; Consumption; Daily; Data; Disease; Endometrial Carcinoma; Epithelial Cells; Epithelium; Estrogen receptor negative; Estrogen receptor positive; Estrogens; Event; Exposure to; Fatty Acids; Fine needle aspiration biopsy; Flax; Food; Gene Mutation; Genes; Growth Factor; Health Benefit; High Risk Woman; Ingestion; Insulin; Intervention; Label; Lead; Lignans; Malignant Neoplasms; Measures; Medical Surveillance; Morbidity - disease rate; New Agents; Numbers; Operative Surgical Procedures; Participant; Personal Satisfaction; Phytoestrogens; Pilot Projects; Population; Premenopause; Proliferating; Public Health; Randomized; Randomized Controlled Clinical Trials; Rate; Recording of previous events; Reporting; Research; Risk; Risk Reduction; S-Phase Fraction; Sampling; Score; Serum; Somatomedins; Source; Staging; Surrogate Endpoint; Tamoxifen; Testing; United States Food and Drug Administration; Vascular Endothelial Growth Factors; Woman; alpha-Linolenic Acid; base; bcl-1 Genes; cancer risk; carcinogenesis; caspase-3; day; estrogenic activity; improved; indexing; malignant breast neoplasm; mortality; pre-clinical; preclinical study; prevent; success; survivin; tumor growth

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.

描述（由申请人提供）： 目前，乳腺癌化学预防使用源自治疗成功的策略，其中治疗相关发病率的阈值较高。许多患乳腺癌的风险较高但目前已无癌症的女性发现类似的发病风险是不可接受的，因此她们选择单独进行监测。在这个健康人群中需要替代策略来化学预防乳腺癌。亚麻籽是一种天然食物来源，含有木酚素（一种植物雌激素）和 α-亚麻酸（一种 omega-3 脂肪酸）。临床前和临床研究显示，食用亚麻籽可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，而且亚麻籽没有已知的严重副作用。拟议进行一项试点研究来检验一个中心假设，即亚麻籽对于乳腺癌高风险的健康绝经前妇女来说将是一种安全有效的化学预防剂。中心假设将通过以下具体目标进行测试：确定每天摄入 25 克磨碎的亚麻籽 1) 是否会改变六个月后随机乳晕周围细针抽吸 (RPFNA) 样本中表达 Ki-67 和 caspase-3（细胞凋亡指标）的乳腺上皮细胞的比例； 2）改变RPFNA样本中雌激素调节基因、细胞周期蛋白D1、生存素和血管内皮生长因子（VEGF）； 3) 六个月后会改变 IGF-1 和 IGFBP-3 的血清水平，4) 对绝经前妇女产生任何显着的副作用，这些妇女根据盖尔和克劳斯评分升高、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抽吸样本的 Ki-67 标记指数 >1.5%，患乳腺癌的风险增加 （RPFNA）。 50 名研究参与者将被随机分配每天服用 25 克亚麻籽粉，或者 6 个月内不接受任何干预。将记录合规性和影响亚麻籽接受度的因素。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 RPFNA 的 Ki-67 标记指数和 caspase-3、雌激素调节基因以及胰岛素生长因子 (IGF)-1 和胰岛素生长因子结合蛋白 (IGFBP)-3 的血清水平。如果这项针对高风险女性的试点研究表明亚麻籽对乳腺癌风险的生物标志物有有利影响并被参与者接受，那么将提出一项更大规模的随机试验来评估磨碎的亚麻籽的消费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，具有许多健康益处且副作用很少。它含有可以通过减少乳房中生长的细胞数量来预防乳腺癌的物质。这项研究将确定亚麻籽是否可以减少患乳腺癌风险较高的年轻女性乳房中生长的细胞数量。