Identifying effective risk-based supplemental ultrasound screening strategies for women with dense breasts

修改项目摘要/摘要部分 乳腺密度是发展乳腺癌的一个危险因素，并降低了筛查性乳房X光检查的准确性。据估计，美国有2700万40-74岁的女性乳房致密，她们的晚期乳腺癌诊断率升高，与不良结局相关。37个州现在要求乳房X光检查机构通知乳房致密的妇女乳房X光检查的局限性，并建议与其医疗保健提供者讨论筛查方案，一项国家法律正在等待通过。在没有致密乳房妇女的筛查指南的情况下，补充性超声波筛查的使用急剧增加，这种筛查广泛使用，直接医疗费用低。早期对辅助超声性能的研究表明，增加了癌症检测，但假阳性检查率高，导致不必要的活检。美国预防服务工作组呼吁进行研究，评估补充超声筛查对有意义的临床结果（如晚期癌症发生率）的影响，以告知致密乳房妇女的筛查指南。我们最近证明，乳房X光检查筛查失败率（即，根据临床风险因素，乳腺密度高的妇女中的晚期癌症和正常乳房X光检查后的间歇性癌症的发生率差别很大。因此，我们建议在一个新的基于风险的框架内评估补充超声筛查的性能。我们假设，针对乳腺X线摄影筛查失败风险高的致密乳腺女性亚组进行补充超声筛查将产生有利的获益-损害特征。我们将使用通过乳腺癌监测联盟收集的超过10万次筛查超声检查和200万次乳腺X线摄影筛查检查的观察数据，根据初步筛查类型检查补充筛查超声的测试性能（目标1（数字乳腺X射线摄影与数字乳腺断层合成摄影）;和（目的2）评估乳腺X线摄影筛查失败风险水平的补充筛查超声结果。这些结果将被用作来自癌症干预和监测建模网络的两个模拟模型的输入，以（目标3）评估针对乳腺X线摄影筛查失败高风险女性的补充超声策略的长期益处、危害和成本。我们的研究将是对补充超声的最大评估，也是第一个根据乳房X线检查筛查失败的风险评估间隔期和晚期癌症的比率。我们的研究结果将为女性，医疗保健提供者和指南制定者提供急需的可操作证据，以评估致密乳房女性的筛查选择。这一证据将支持有效的补充筛查策略，以减轻乳腺X线筛查不足的妇女的乳腺癌负担，同时最大限度地减少潜在的危害。

Modified Project Summary/Abstract Section Breast density is a risk factor for developing breast cancer and decreases the accuracy of screening mammography. An estimated 27 million women aged 40-74 in the U.S. have dense breasts and they experience elevated rates of advanced stage breast cancer diagnoses associated with poor outcomes. Thirty-seven states now require mammography facilities to notify women with dense breasts of the limitations of mammography and recommend discussion of screening options with their healthcare providers, and a national law is pending. In the absence of screening guidelines for women with dense breasts, there has been a dramatic increase in use of supplemental ultrasound screening, which is widely available and has low direct medical costs. Early studies of supplemental ultrasound performance suggest increased cancer detection but high rates of false positive exams leading to unnecessary biopsies. The United States Preventive Services Task Force has called for studies that evaluate the impact of supplemental ultrasound screening on meaningful clinical outcomes, such as advanced cancer rates, to inform screening guidelines for women with dense breasts. We recently demonstrated that mammography screening failure rates (i.e., advanced cancers and interval cancers after a normal mammogram) among women with dense breasts vary widely according to clinical risk factors. Therefore, we propose to assess supplemental ultrasound screening performance within a new risk-based framework. We hypothesize that supplemental ultrasound screening targeted to the subset of women with dense breasts at high risk of mammography screening failures will yield a favorable benefit-to-harm profile. We will use observational data from more than 100,000 screening ultrasound exams and 2 million mammography screening exams collected via the Breast Cancer Surveillance Consortium to (Aim 1) examine the test performance of supplemental screening ultrasound according to type of primary screening (digital mammography vs. digital breast tomosynthesis); and (Aim 2) evaluate supplemental screening ultrasound outcomes across levels of risk for mammography screening failures. These results will be used as inputs in two simulation models from the Cancer Intervention and Surveillance Modeling Network to (Aim 3) evaluate the long-term benefits, harms, and costs of supplemental ultrasound strategies targeted to women at high risk of mammography screening failures. Our study will be the largest evaluation of supplemental ultrasound and the first to evaluate rates of interval and advanced cancers according to risk of mammography screening failures. Our results will provide urgently needed, actionable evidence for women, healthcare providers, and guideline-makers evaluating screening options for women with dense breasts. This evidence will support effective supplemental screening strategies that reduce the burden of breast cancer among women for whom mammography screening is not adequate, while minimizing potential harms.