The Effects of Vitamin D on Mammographic Density and Breast Tissue

描述(申请人提供)：乳房X光摄影密度是乳腺癌的最大危险因素之一。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记物。几个州现在强制向女性发布乳房X光检查密度数据。然而，除了抗荷尔蒙疗法(如他莫昔芬)外，还没有任何干预措施被证明可以降低乳房密度。因此，测试有希望的、耐受性良好的干预措施，可能会影响乳房X光检查密度，这是非常有意义的。一些证据表明，维生素D可能在乳房密度和乳腺癌的发生中起作用。维生素D可抑制乳腺细胞的增殖，促进乳腺细胞的分化和凋亡。然而，还没有大规模的随机研究来检验维生素D对乳房X光照相密度的影响。我们建议在NIH赞助的维生素D和omega-3试验(VITAL)中检验维生素D3对乳房X光摄影的随机影响，这是一项正在进行的随机双盲试验，测试维生素D3(每天2,000 IU胆钙醇)和omega-3脂肪酸(840毫克二十碳五烯酸[EPA]+二十二碳六烯酸[DHA])在超过24,000名男性和女性多种族人口中对癌症和心血管疾病的一级预防作用。在这项辅助性次级研究中，将对4000名年龄在55-67岁(25%为非裔美国人)的女性进行乳房X光检查，从基线(随机前)开始，以及在随机治疗1年和4年后进行。将测量中央处理的定量乳房X光照相密度和纹理变化。我们将确定随机维生素D治疗是否与乳房X光检查特征的改变有关，以及影响是否受到基线乳房X光检查密度和基线25(OH)维生素D水平的影响。此外，还将收集正在接受乳房活组织检查/手术的女性的组织样本，包括非恶性和恶性两种情况。与安慰剂相比，服用随机维生素D3的妇女收集的组织将进行定量的形态测量，以及针对维生素D激活和乳腺癌发生途径的基因表达分析。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设置下全面测试维生素D3对乳房X光检查特征和乳房组织生物学的影响。

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.