Evaluation of 3D MRI-Based Quantitative Breast Density for Chemoprevention

描述(由申请人提供)： 乳房X光照相密度被广泛认为是乳腺癌的危险因素。乳房X光照相密度测量存在许多缺点。乳房X光摄影是投影的2D图像，而不是3D图像。乳房X光检查存在参数校准不完善和胶片曝光系数变化的问题。曝光、压缩和冲洗化学成分的变化可能会影响胶片的背景密度，并可能影响每项研究中测量的乳房密度，从而使受试者之间或纵向上的比较不可靠。在乳腺MRI上测量的密度具有很大的潜力，可以提供一种敏感的、定量的方法来评估乳腺密度。MRI提供了区分纤维腺和脂肪组织的强大软组织对比度；它还提供了乳房的三维覆盖；因此是评估纤维腺密度的最佳成像方式。尽管有几项研究使用了MRI，旨在开发自动化的计算机辅助乳房X光照相密度分析，但几乎没有努力开发一种可靠的方法来监测单个女性随着时间的推移乳房密度的变化。一种基于MRI的“纤维腺体密度百分比”的定量测量可以用来评估化学预防药物引起的变化。二级化学预防通常用于已被诊断为乳腺癌的高危女性。乳腺癌治疗后，对侧乳房的乳腺癌发病率增加。20年累积发病率为15.4%。他莫昔芬被证明是有效的，并被广泛应用于被诊断为雌激素受体阳性的绝经前乳腺癌患者。尽管结果令人振奋，但是否提供化学预防，或给予哪种药物，完全取决于人口研究结果。没有一种个性化的方法可以用来让女性确定化学预防是否对她有效，因此对可能的副作用和风险是有益的。在这项应用中，我们建议使用我们开发的基于3D MRI的定量乳房密度评估方法来测试特定的假设，即使用他莫昔芬进行二次化学预防(针对绝经前妇女)将比对照降低乳房密度。我们还将跟踪所有登记的受试者，以了解未来乳腺癌的发展情况。当数据可用时，我们将能够直接检验密度降低与未来癌症事件减少相关的假设。这项研究提出了两个目标：1)目的1：利用基于MRI的分析，评估接受他莫昔芬治疗的绝经前妇女与对照组的乳房密度的变化。2)目的-2：获取所有患者的乳腺X线片进行密度分析，并将测量结果与MRI结果进行比较，比较他莫昔芬与对照组之间的测量差异和密度变化。

DESCRIPTION (provided by applicant): Mammographic density is well accepted as a risk factor for breast cancer. Many drawbacks exist for mammographic density measurements. Mammography is a projection 2D image, not a 3D image. Mammography suffers from imperfect calibration of parameters and variation in film exposure factors. Changes in exposure, compression, and processor chemistry may influence the background density of the film and potentially the measured breast density in each study, making comparison between subjects or longitudinally unreliable. Density measured on breast MRI has a great potential to provide a sensitive, quantitative method for evaluating breast density. MRI provides a great soft tissue contrast distinguishing between fibroglandular and fatty tissues; also it provides the 3-dimensional breast coverage; thus is an optimal imaging modality for evaluating fibroglandular density. Despite several studies used MRI aiming for developing automated computer-aided mammographic density analysis, there is little effort to develop a reliable method for monitoring the change breast density over time for individual woman. A quantitative MRI-based measure of "percent fibroglandular density" may be used to evaluate the changes induced by the chemoprevention drug. Secondary chemoprevention is commonly used for high-risk women who already had diagnosis of breast cancer. Incidence of breast cancer in the contralateral breast increases after treatment of breast caner. The cumulative incidence at 20 years was 15.4%. Tamoxifen was proven effective, and prescribed widely to pre-menopausal patients diagnosed with estrogen receptor positive breast cancer. Despite the promising results, whether to offer chemoprevention, or which drug to give, is solely based on population study results. There is not an individualized method that can be used for a woman to determine whether the chemoprevention is working on her, thus is beneficial over the possible side effects and risks. In this application we propose to use our developed 3D MRI-based quantitative breast density evaluation method to test the specific hypothesis that secondary chemoprevention with tamoxifen (for pre-menopausal women) will reduce the breast density compared to controls. We will also follow all enrolled subjects for future events of breast cancer development. When the data is available we will be able to directly test the hypothesis that reduced density is correlated with lower future cancer events. Two aims are proposed in this study 1) Aim-1: To evaluate the changes of breast density in pre-menopausal women receiving tamoxifen vs. controls using MRI-based analysis. 2) Aim-2: To obtain mammograms of all patients for density analysis, and compare the results to that based on MRI in terms of measurement variation and changes of density between tamoxifen vs. controls.