Role of Advanced Screening Technologies in Early Detection of Breast Cancer

描述（由申请人提供）：先进筛查技术在乳腺癌早期检测中的作用项目摘要/摘要本申请涉及广泛的挑战领域（05）：比较有效性研究和特定的挑战主题，05-CA-105 CISNET（癌症干预和监测建模网络）。这项研究的目标是评估与先进的乳腺癌筛查技术相关的益处。计划应用Lee和Zelen（2008）开发的随机模型，以解决先进筛查技术在乳腺癌早期检测中的有效性。Lee-Zelen模型（2008）已作为CISNET乳腺组的一部分开发。该模型预测乳腺癌死亡率作为疾病自然史和检测过程的函数。该模型的主要假设是：i）乳腺癌是一种进行性疾病，ii）筛查的死亡率受益是由于诊断的阶段转变。在迅速兴起的先进筛查技术中，据报道数字乳腺X射线摄影（DM）和磁共振成像（MRI）在诊断乳腺癌方面更敏感。然而，与这些筛查方式相关的死亡率获益尚未进行评估。该补助金将重点评估糖尿病和MRI筛查的死亡率效益。数字乳房X线摄影成像筛查试验显示，在筛查50岁以下的女性或具有非常致密乳房的任何年龄的女性时，DM比胶片乳房X线摄影显著更敏感（Pisano等人，2005年）的报告。在检测具有乳腺癌遗传易感性的女性中的乳腺癌方面，MRI已经显示出比乳房X线照相术更敏感（Kreige等人，2004; Leach等人，2005年）的报告。一个重要的问题，这将是调查处理最佳的筛选策略，使用DM和MRI。筛查程序的特征在于：i）开始筛查程序的年龄，ii）检查之间的时间和3）可能的结束筛查的年龄。这些变量有很多潜在的排列，临床试验不可能检查所有可能的排列。此外，随机试验是不可行的。调查这个问题的唯一方法是建立一个筛查过程的分析模型，其中包括疾病和筛查过程的主要特征。基于风险的筛查计划的潜在节省是巨大的。具体而言，计划：估计50岁以下女性和任何年龄的致密乳房女性的糖尿病死亡率获益。估计糖尿病在美国人群中传播的潜在死亡率获益。评估MRI在乳腺癌风险升高的女性中的死亡率获益。找到最佳的筛查检查时间表，这取决于乳腺密度。根据DM和MRI筛查模式的风险状态研究最佳筛查策略。先进的筛查技术在早期发现乳腺癌中的作用 公共卫生相关性：磁共振成像（MRI）可用于高风险人群的乳腺癌筛查，数字乳房X线摄影术可有利于筛查乳腺致密的女性。该项目将使用Lee-Zelen（2008）的数学模型来评估死亡率效益，并为这些先进的筛查模式找到最佳的筛查策略。由于很难使用随机临床试验来研究这些问题，数学模型可以在理解这些筛选方式的潜在收益方面做出重大贡献。

DESCRIPTION (provided by applicant): Role of Advanced Screening Technologies for Early Detection of Breast Cancer Project Summary/Abstract This application addresses broad Challenge Area (05): Comparative Effectiveness Research and specific Challenge Topic, 05-CA-105 CISNET (The Cancer Intervention and Surveillance Modeling Network). The goals of this research are targeted at evaluating the benefits associated with advanced screening technologies for breast cancer screening. It is planned to apply the stochastic model developed by Lee and Zelen (2008) to address the effectiveness of advanced screening technologies in the early detection of breast cancer. The Lee-Zelen model (2008) has been developed as part of the CISNET breast group. The model predicts breast cancer mortality as a function of the disease natural history and detection process. The principal assumptions of the model are that: i) breast cancer is a progressive disease and ii) mortality benefit from screening is due to a stage shift in diagnosis. Among the rapidly emerging advanced screening technologies, digital mammography (DM) and magnetic resonance imaging (MRI) have been reported to be more sensitive in diagnosing breast cancer. However the mortality benefit associated with these screening modalities has not been evaluated. This grant will focus on evaluating the mortality benefit from DM and MRI screening. The digital mammographic imaging screening trial showed that DM was significantly more sensitive than film mammography in screening women under age 50 or women of any age with very dense breasts (Pisano et al., 2005). MRI has been shown to be more sensitive than mammography in detecting breast cancer in women with inherited susceptibility to breast cancer (Kreige et al., 2004; Leach et al., 2005). An important issue which will be investigated deals with optimal screening strategies using DM and MRI. A screening program is characterized by: i) the age to begin a screening program, ii) the times between examinations and 3) possibly the age to end screening. There are so many potential permutations of these variables that clinical trials cannot possibly examine all of the possible permutations. Furthermore randomized trials are not feasible. The only way to investigate the problem is to have an analytical model of the screening process which incorporates the main features of the disease and the screening process. The potential savings of having screening programs based on risk are enormous. Specifically it is planned to: Estimate the mortality benefit of DM in women under age 50 and women of any age with dense breasts. Estimate the potential mortality benefit of DM if disseminated in the U.S. population. Estimate the mortality benefit of MRI in women with elevated risk of developing breast cancer. Find optimal screening exam schedules which depend on breast density. Investigate optimal screening strategies by risk status for DM and MRI screening modalities. Role of Advanced Screening Technologies for Early Detection of Breast Cancer PUBLIC HEALTH RELEVANCE: Magnetic resonance imaging (MRI) may be utilized for breast cancer screening in high risk populations and digital mammography may be advantageous for screening women with dense breasts. This project will use the Lee-Zelen's (2008) mathematical model to evaluate mortality benefit as well as to find optimal screening strategies for these advanced screening modalities. As it is difficult to investigate these problems using randomized clinical trials, mathematical models can make a significant contribution in understanding the potential gain from these screening modalities.