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

描述（由申请人提供）： 乳腺摄影密度被公认为乳腺癌的一个危险因素。乳房摄影密度测量存在许多缺点。乳房X线摄影是一种投影2D图像，而不是3D图像。乳房X线照相术遭受参数的不完美校准和胶片曝光因子的变化。曝光、压缩和处理器化学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腺密度，从而使受试者之间的比较或纵向不可靠。在乳腺MRI上测量的密度具有很大的潜力，可以为评估乳腺密度提供一种灵敏的定量方法。MRI提供了区分纤维腺体和脂肪组织的良好软组织对比;它还提供了三维乳腺覆盖;因此是评价纤维腺体密度的最佳成像方式。尽管有几项研究使用MRI旨在开发自动化计算机辅助乳腺摄影密度分析，但几乎没有努力开发一种可靠的方法来监测个体女性乳腺密度随时间的变化。基于MRI的定量测量“纤维腺体密度百分比”可用于评估化学预防药物诱导的变化。二级化学预防通常用于已经诊断出乳腺癌的高危女性。乳腺癌治疗后，对侧乳腺的乳腺癌发病率增加。20年时的累积发生率为15.4%。他莫昔芬被证明是有效的，并广泛用于绝经前诊断为雌激素受体阳性乳腺癌的患者。尽管结果令人鼓舞，但是否提供化学预防，或者给予哪种药物，完全是基于人群研究结果。没有一种个性化的方法可以用于女性来确定化学预防是否对她起作用，因此对可能的副作用和风险有利。在本申请中，我们建议使用我们开发的基于3D MRI的定量乳腺密度评估方法来测试特定的假设，即与对照组相比，他莫昔芬（用于绝经前妇女）的二次化学预防将降低乳腺密度。我们还将随访所有入组受试者的未来乳腺癌发生事件。当数据可用时，我们将能够直接测试密度降低与未来癌症事件降低相关的假设。本研究提出了两个目的：1）目的-1：使用基于MRI的分析评价接受他莫昔芬与对照组的绝经前妇女乳腺密度的变化。2)目标二：获得所有患者的乳腺X线片进行密度分析，并将其结果与基于MRI的结果进行比较，比较三苯氧胺与对照组之间的测量变异和密度变化。

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.