New Risk Assessment Paradigm to Predict Screening Detection, Failures and False Alarms

项目概要-项目1 2016年美国预防服务工作组和2015年美国癌症协会指南呼吁降低筛查强度，并要求提供者与女性讨论她们对筛查的偏好。这种对个性化决策的推动已经引发了基于风险的筛查利用的实质性进展，这种筛查利用不仅仅依赖于女性的年龄来确定何时开始和停止筛查或筛查频率。然而，将风险评估明确纳入一般人群的筛查指南仍处于早期阶段。风险预测是基于风险的筛查的一个关键方面;现有的模型预测乳腺癌的总体风险，但没有考虑到乳腺癌生物学的异质性或筛查模式检测乳腺癌的能力。项目1旨在推进一种新的基于风险的筛查模式，确定妇女的筛查检测，失败和假警报的绝对累积风险，同时明确考虑筛查间隔和使用的方式。 1）利用现有的和扩展的乳腺癌监测联盟（BCSC）基础设施，项目研究人员将开发新的风险预测模型，以识别处于以下高风险的女性：1）早期筛查发现的癌症（I/IIa期浸润性癌症），2）筛查失败（间隔浸润性癌症或筛查发现的IIb期或更高），以及3）假警报（假阳性测试和良性活检）。使用BCSC数据超过1，000，000名年龄在40-79岁之间的女性接受数字乳腺X射线摄影或断层合成摄影，以及超过13，000例浸润性乳腺癌，该项目团队将确定与影响筛查结果的乳腺癌风险相关的临床和成像因素，为每年，两年和三年的筛查方案的每个筛查结果生成六年的风险估计。 目标2）项目组将使用妇女和临床医生调查和德尔菲小组确定筛查失败和误报的临床有意义风险的可操作水平，以及相关的长期筛查结果。 这一建议将回答：1）哪些女性筛查失败的风险较高，需要两年一次的乳房X光检查的替代策略，哪些女性风险较低，可以不经常进行筛查？2)不良筛查结果的风险水平如何影响女性和临床医生对筛查策略的偏好？ 该项目将提供证据，指导妇女、卫生保健提供者和政策制定者根据筛查失败和假警报的短期风险制定筛查策略，旨在改善侵袭性肿瘤的早期检测，同时最大限度地减少危害。

PROJECT SUMMARY – Project 1 The 2016 US Preventive Services Task Force and 2015 American Cancer Society guidelines call for reduced screening intensity and for providers to discuss with women their preferences for screening. This push for individualized decision-making has triggered substantial movement toward risk-based screening utilization that does not rely solely on a woman's age to determine when to start and stop screening or screening frequency. Yet, the explicit incorporation of risk assessment into screening guidelines for the general population is in its early stages. Risk prediction is a key aspect of risk-based screening; available models predict breast cancer risk overall, but do not take into account the heterogeneity of breast cancer biology or the ability of screening modalities to detect breast cancer. Project 1 aims to advance a new risk-based screening paradigm that identifies women's absolute cumulative risk of screening detection, failures, and false alarms while explicitly considering screening interval and modality used. Aim 1) Using the existing and expanded Breast Cancer Surveillance Consortium (BCSC) infrastructure, project investigators will develop new risk prediction models to identify women at high risk of: 1) early-stage screen-detected cancer (stage I/IIa invasive cancer), 2) screening failure (interval invasive cancer or screen-detected stage IIb or higher), and 3) false alarms (false-positive tests and benign biopsies). Using BCSC data on over 1,000,000 women aged 40-79 years undergoing digital mammography or tomosynthesis, and over 13,000 invasive breast cancers identified, the project team will identify clinical and imaging factors associated with breast cancer risk that impact screening outcomes, generating six-year risk estimates for each screening outcome for annual, biennial, and triennial screening regimens. Aim 2) The project team will identify actionable levels of clinically-meaningful risk of screening failure and false alarm, and associated long-term screening outcomes using women and clinician surveys and Delphi panels. This proposal will answer: 1) Which women are at high risk of screening failures and require an alternative strategy to biennial mammography, and which women are at low risk and can be screened less often? 2) What risk levels of poor screening outcomes impact women and clinician preferences for screening strategies? This project will provide evidence to guide women, health care providers, and policymakers on screening strategies based on short-term risk of screening failures and false alarms with the goal to improve early detection of aggressive tumors while minimizing harms.