FlaxSeed Lignan for Breast Cancer Chemoprevention

亚麻籽木脂素用于乳腺癌的化学预防

• 批准号: 7250166
• 负责人: CAROL J. FABIAN
• 金额: $ 14.56万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-12 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7250166
• 关键词: Address; Benign; Binding Proteins; Biological Markers; Breast; Cells; Chemoprevention; Clinical Chemoprevention; Cohort Studies; Development; Ductal Epithelium; Enrollment; Epidemiologic Studies; Epithelial Cells; Fine needle aspiration biopsy; Flax; Future; High Risk Woman; Hyperplasia; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Ki-67 Antigen; Lignans; Mammographic Density; Measurement; Phase; Pilot Projects; Placebo Control; Plasma; Premenopause; Prevention; Principal Investigator; Risk; Sample Size; Serum; Source; Specimen; Staining method; Stains; Woman; base; breast density; cancer risk; design; enterodiol; flaxseed lignan; malignant breast neoplasm; programs; randomized placebo controlled trial; secoisolariciresinol

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：目的是在乳腺癌发育高风险的女性中进行原则研究证明，评估亚麻籽中高水平中发现的天然木质。木质烯的来源将是商业产品Brevail（200 mg），它始终提供50毫克的Secoisolariciresinol diglycoside（SDG）和由此产生的血清肠内肠痛水平与乳腺癌的降低相关的流行病学研究。我们将评估几种与增加乳腺癌风险相关的生物标志物，包括通过随机的外围细胞抽吸（FNA），乳房X线X乳乳腺密度，胰岛素样生长因子I（IGF-1）的血清水平及其结合蛋白IGFBP-3，在Brev的基线和12个月后获得的胰岛素样生长因子I（IGF-1）获得的增生性导管上皮增殖。这些风险生物标志物的变化将与血清肠痛和肠二醇水平的变化相关。可以预计，在FNA上具有足够的细胞产量，至少有2％的Ki-67阳性细胞将纳入该试验研究。研究的目的包括：1）表达增殖抗原Ki-67的良性上皮细胞比例的变化； 2）乳房X线摄影密度变化； 3）更改血清IGF-1/IGFBP-3； 4）测量血清可持续发展目标，肠阳离子和肠二醇水平，以及与风险生物标志物的调节相关。这项研究将为这些风险生物标志物的12个月内的变化幅度提供估计，这将为未来更大的安慰剂受控随机试验提供样本量计算的基础。这项研究将提供初步证据表明，如果血清肠内甲醇水平保持在34 nm以上，那么乳腺癌高风险的绝经前妇女是否可能受益。如果肯定，这项研究的结果对于使用Brevail和/或商业亚麻籽的安慰剂对照II期预防试验的设计和实施至关重要。