The Effects of Vitamin D on Mammographic Density and Breast Tissue

描述（由申请人提供）：乳腺摄影密度是乳腺癌最强的风险因素之一。它可以预测未来至少10年的乳腺癌风险，并已被建议作为乳腺癌风险的替代标志物。一些州现在要求向妇女公布乳房X线摄影密度数据。然而，除了抗激素治疗（例如，他莫昔芬），没有干预措施已被证明可以降低乳腺密度。因此，测试有希望的，耐受性良好的干预措施，可能会影响乳腺摄影密度是非常感兴趣的。一些证据表明，维生素D可能在乳腺密度和乳腺癌发生中发挥作用。维生素D可减少培养物中乳腺细胞的增殖并促进其分化和凋亡。然而，还没有大规模的随机研究研究维生素D对乳腺摄影密度的影响。我们建议在NIH赞助的Vitamin D和OmegA-3 TriaL（VITAL）中检查维生素D3对乳房X线摄影乳腺密度的随机效应，这是一项正在进行的随机、双盲、试验，测试维生素D3（二、000 IU/天胆钙化醇）和ω-3脂肪酸（840毫克二十碳五烯酸[EPA]+二十二碳六烯酸[DHA]）在癌症和心血管疾病的一级预防中的多重作用，有24，000多名男性和女性。在这项辅助子研究中，将从基线（随机化前）以及随机化治疗1年和4年后对4000名年龄为55-67岁（25%为非洲裔美国人）的女性进行乳房X线检查。将测量集中处理的定量乳腺摄影密度和纹理变化。我们将确定随机维生素D治疗是否与乳腺X线摄影特征的变化相关，以及基线乳腺X线摄影密度和基线25（OH）维生素D水平是否会改变效果。此外，还将采集VITAL中接受乳腺活检/手术（非恶性和恶性疾病）的女性的组织样本。将对随机服用维生素D3与安慰剂的女性中收集的组织进行定量形态学测量，以及针对维生素D激活和乳腺癌发生途径的基因表达测定。这项辅助研究提供了一个及时的机会，以最小的额外成本在随机环境中全面测试维生素D3对乳房X线摄影特征和乳腺组织生物学的影响。

DESCRIPTION (provided by applicant): Mammographic density is one of the strongest risk factors for breast cancer. It is predictive of breast cancer risk for at least 10 years in the futue and has been suggested as a surrogate marker of breast cancer risk. Several states now mandate release of mammographic density data to women. However, except for anti-hormonal therapies (e.g., tamoxifen), no interventions have been proven to reduce breast density. Thus, testing promising, well-tolerated interventions that might affect mammographic density is of substantial interest. Several lines of evidence suggest that vitamin D may play a role in breast density and breast carcinogenesis. Vitamin D reduces proliferation and promotes differentiation and apoptosis in breast cells in culture. However, no large-scale randomized studies have examined the impact of vitamin D on mammographic density. We propose to examine the randomized effects vitamin D3 on mammographic breast density in the NIH sponsored VITamin D and OmegA-3 TriaL (VITAL), an ongoing randomized, double blind, trial testing vitamin D3 (2,000 IU/day cholecalciferol) and omega-3 fatty acids (840 mg eicosapentaenoic acid [EPA]+ docosahexaenoic acid [DHA]) in the primary prevention of cancer and cardiovascular disease in a multi-ethnic population of over 24,000 men and women. In this ancillary sub study, mammograms will be obtained on 4000 women age 55-67 years (25% African-American), from baseline (pre-randomization) and after 1 and 4 years of randomized therapy. Centrally processed quantitative mammographic density and texture variation will be measured. We will determine if randomized vitamin D treatment is associated with change in mammographic features, and whether effects are modified by baseline mammographic density, and baseline 25(OH) vitamin D levels. In addition, tissue samples from women in VITAL undergoing breast biopsy/surgery, for both nonmalignant and malignant conditions, will be collected. Quantitative morphological measures, as well as gene expression assays targeting vitamin D activation and breast carcinogenesis pathways, will be performed on collected tissues among women on randomized vitamin D3 compared with placebo. This ancillary study provides a timely opportunity to test comprehensively the effects of vitamin D3 on mammographic features and breast tissue biology in a randomized setting at minimal additional cost.