MRI Background Parenchymal Enhancement as a Risk Factor for Breast Cancer

描述（由申请人提供）：对比增强乳房磁共振成像（MRI）是一种临床有用的工具，用于高风险妇女的乳腺癌筛查和乳腺癌患者的诊断、分期和临床管理，也可能在确定乳腺癌风险方面发挥作用。正常乳腺纤维腺组织（FGT）在乳房x光摄影上呈白色（即乳房x光密度（MD）），是公认的乳腺癌危险因素。在乳腺MRI （MRI-FGT）上也可见FGT，并在给予MRI造影剂后不同程度地增强（变亮）。背景实质增强（MRI-BPE）是对这种增强的体积和强度的测量。在一项对39例乳腺癌患者和78例无癌对照者进行MRI乳房筛查的研究中，MRI- bpe与乳腺癌风险密切相关；与MRI-BPE最低组相比，MRI-BPE最高组的女性患乳腺癌的风险高7.5倍。MRI-BPE与MRI-FGT仅呈弱相关，而MRI-FGT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志。我们将在三个中心招募、访谈和收集1110名浸润性乳腺癌女性（病例）和1110名无癌且正在接受MRI乳腺癌筛查的高风险女性（对照组）的医疗记录、治疗前核磁共振成像和乳房x线照片。通过电子病历审核提取临床资料和肿瘤特征（病例）。MRI-BPE和MRI-FGT将由单个阅读器使用标准临床测量和乳房x线摄影百分比密度（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，MRI-FGT和MPD测量的是FGT的数量，而MRI-BPE是乳腺组织活动的标志，与存在的FGT的数量无关，它对乳腺癌风险的影响是独立的。我们的主要目的是研究通过乳腺成像报告和数据系统（BI-RADS）分类测量的MRI-BPE和MRI-FGT与乳腺癌风险之间的关系。我们的次要目的是：1)确定与单独MPD相比，纳入MRI-BPE是否能改善乳腺癌风险评估；2)检查MRI-BPE和MRI-FGT之间的关系，通过一种新的自动化计算机化方法在连续尺度上测量，与乳腺癌风险。从长期来看，MRI- bpe可以通过确定从强化筛查和预防措施中获益最多的女性亚组以及可能从低强度筛查中获益的低风险女性亚组，大大提高接受乳房MRI筛查的高风险女性乳腺癌风险预测的准确性。MRI-BPE和MRI-FGT的自动化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.