MRI Background Parenchymal Enhancement as a Risk Factor for Breast Cancer

描述(申请人提供)：对比度增强的乳腺磁共振成像(MRI)是一种临床上有用的工具，用于高危女性的乳腺癌筛查以及乳腺癌患者的诊断、分期和临床处理，也可能在确定乳腺癌风险方面有实用价值。正常乳腺纤维腺组织(FGT)在乳房X光检查中呈白色(即乳房X光密度(MD))，是乳腺癌的公认危险因素。FGT在乳腺MRI(MRI-FGT)上也可见，并在注射MRI造影剂后不同程度地增强(变得更亮)。背景实质性增强(MRI-BPE)是对增强的体积和强度的测量。在一项对39例乳腺癌患者和78名无癌对照进行MRI乳房筛查的研究中，MRI-BPE与乳腺癌风险密切相关；MRI-BPE级别最高的女性患乳腺癌的风险是MRI-BPE级别最低的女性的7.5倍。MRI-BPE仅与MRI-FGT呈弱相关，而与MD呈强相关，提示MRI-BPE可能是乳腺癌风险的独立标志物。我们建议通过开展一项多中心、以医院为基础的病例对照研究来证实这些发现，该研究将MRI-BPE和MRI-FGT作为乳腺癌风险的标记物。我们将通过三个中心招募、面试和收集1110名浸润性乳腺癌女性(病例)和1110名正在接受MRI乳腺癌筛查(对照)的高危女性的医疗记录和治疗前核磁共振成像和乳房X光检查。将通过电子病历审查提取临床数据和肿瘤特征(针对病例)。MRI-BPE和MRI-FGT将由单一阅读器使用标准临床测量和使用Cumulus的乳房X光摄影百分比密度(MPD)进行评分。我们还建议使用一种新的全自动方法来测量MRI-BPE和MRI-FGT。我们的假设是，虽然MRI-FGT和MPD测量FGT的数量，但MRI-BPE是乳腺组织活动的标志，与存在的FGT的数量无关，对乳腺癌风险的贡献。我们的主要目的是研究MRI-BPE和MRI-FGT(BI-RADS)分类测量的MRI-BPE和MRI-FGT与乳腺癌风险的关系。我们的次要目标是：1)确定纳入MRI-BPE是否比单独使用MPD更能改善乳腺癌风险评估；以及2)通过一种新的自动化计算机方法在连续范围内测量MRI-BPE和MRI-FGT与乳腺癌风险的关联。从长远来看，MRI-BPE可以通过确定将从加强筛查和预防措施中受益最大的一组妇女，以及可能从较低风险筛查中受益的一组低风险妇女，极大地提高接受乳腺MRI筛查的高危妇女乳腺癌风险预测的准确性。MRI-BPE和MRI-FGT的自动定量测量将极大地促进将这些测量纳入广泛的临床和研究实践。

DESCRIPTION (provided by applicant): Contrast-enhanced breast magnetic resonance imaging (MRI) is a clinically useful tool for breast cancer screening in high-risk women and the diagnosis, staging, and clinical management of breast cancer patients, and may also have utility in the determination of breast cancer risk. Normal breast fibroglandular tissue (FGT), which appears white on mammography (i.e. mammographic density (MD)), is a well-established risk factor for breast cancer. FGT is also visible on breast MRI (MRI-FGT) and enhances (becomes brighter) to varying extents after administration of MRI-contrast medium. Background parenchymal enhancement (MRI-BPE) is a measure of the volume and intensity of this enhancement. In a study of 39 breast cancer cases and 78 cancer- free controls undergoing breast screening with MRI, MRI-BPE was strongly associated with breast cancer risk; women in the highest MRI-BPE category had a 7.5-fold higher risk of breast cancer compared with those in the lowest MRI-BPE groups. MRI-BPE only weakly correlated with MRI-FGT, which is strongly correlated with MD, indicating that MRI-BPE may be an independent marker of breast cancer risk. We propose to confirm these findings by conducting a multi-center, hospital-based, case-control study examining MRI-BPE and MRI-FGT as markers of breast cancer risk. Across three centers we will recruit, interview, and collect medical records and pre-treatment MRIs and mammograms from 1,110 women with invasive breast cancer (cases) and 1,110 high- risk women who are cancer-free and are undergoing MRI breast cancer screening (controls). Clinical data and tumor characteristics (for cases) will be abstracted through electronic medical record review. MRI-BPE and MRI-FGT will be scored by a single reader using standard clinical measures and mammographic percent density (MPD) using Cumulus. We also propose to measure both MRI-BPE and MRI-FGT using a new fully automated method. Our hypothesis is that while MRI-FGT and MPD measure the amount of FGT, MRI-BPE is a marker of breast tissue activity, contributing to breast cancer risk independently of the amount of FGT present. Our Primary Aim is to examine the relationship between MRI-BPE and MRI-FGT measured by Breast Imaging-Reporting and Data System (BI-RADS) categories, and breast cancer risk. Our Secondary Aims are: 1) to determine whether the inclusion of MRI-BPE improves breast cancer risk assessment over that achieved by MPD alone; and 2) to examine the association between MRI-BPE and MRI-FGT, measured on a continuous scale by a novel automated computerized method, and breast cancer risk. In the long-run MRI-BPE could greatly improve the accuracy of breast cancer risk prediction among high-risk women undergoing breast MRI screening by identifying a subgroup of women who would benefit the most from heightened screening and preventive measures and possibly a subgroup of women at lower risk who may benefit from less intensive screening. The automated quantitative measures of MRI-BPE and MRI-FGT would greatly facilitate the incorporation of these measures into widespread clinical and research practice.