Comparative Modeling of Precision Breast Cancer Control Across the Translational Continuum

摘要 Cisnet乳房工作组(BWG)建议以新的精度为重点的创新建模研究 有望重新定义乳腺癌控制最佳实践的肿瘤学范例。我们选择了 建模适合填补证据空白并促进临床和政策转换的重要主题。 我们方法的独特组成部分包括对疾病的绝对风险进行建模，以考虑多种风险 因素，解决重要的合并症--特别是2型糖尿病--影响疾病风险和 生存，探索新兴的基于生物标记物的筛查方法，提供以下方面的指导 精确的系统性治疗及其对幸存者生活质量的影响，以及调查种族差异。 具体目标是：1)评估新的精密筛选方法的影响；2)评估 精确治疗模式在辅助、新辅助和转移环境中的影响；3)综合 目标1和2量化精确筛查和精确治疗对美国乳腺癌的贡献 减少死亡率；以及4)提供证据，通过量化来指导减少种族差距的干预措施 影响差异的多种风险、筛查、治疗和生存因素。这项工作的范围不会是 在没有六款独特的BWG车型的情况下可行：Dana Farber(D)，Erasmus(E)，Georgetown- 爱因斯坦(GE)、MD安德森(M)、斯坦福(S)和威斯康星-哈佛(W)。目标包括多个RFA 优先领域，我们已拨出快速反应资金，以解决剩余的优先领域，支持 跨癌症的CISNet协作，并促进初级职业发展。每个目标包括三个或更多目标 模范小组因其独特的结构而被选中，包括外部合作者和初级调查人员。 这些模型将共享公共输入并提供一组标准的收益结果(例如，远程 避免复发和死亡，降低死亡率，远距离无病生存，以及生命年数和质量- 调整寿命)、危害(例如假阳性和良性活检、间歇性癌症、晚期 诊断、过度诊断和治疗对生活质量的影响)和费用。为过去持续提供资金 19年来，建模团队发表了204篇研究论文，为公共卫生政策决策和 培训了13名初级调查员。对于这项提议，BWG将与美国癌症协会 美国放射学会、美国临床肿瘤学会、乳腺癌监测 财团，以及其他。经验丰富的协调中心提供支持项目的基础设施 目标包括资源共享和模型可访问性。不同寻常的环境提供了 前所未有的协同效应和利用资源来解决新的研究问题和支持职业生涯 发展，否则是不可能的。总体而言，这项研究将推进建模研究和 引导乳腺癌控制政策。

ABSTRACT The CISNET Breast Working Group (BWG) proposes innovative modeling research focused on new precision oncology paradigms that are expected to re-define breast cancer control best practices. We selected significant topics where modeling is suited to fill evidence gaps and facilitate clinical and policy translation. Unique components of our approach include modeling of absolute risk of disease accounting for multiple risk factors, addressing important comorbidities—specifically type 2 diabetes—that affect both disease risk and survival, exploring emerging biomarker-based approaches for screening, providing guidance regarding precision systemic treatments and their impact on quality of life in survivors, and investigating race disparities. The specific aims are to: 1) Evaluate the impact of novel precision screening approaches; 2) Evaluate the impact of precision treatment paradigms in the adjuvant, neo-adjuvant, and metastatic setting; 3) Synthesize Aims 1 and 2 to quantify the contributions of precision screening and precision treatment to US breast cancer mortality reductions; and 4) Provide evidence to guide interventions to reduce race disparities by quantifying multiple risk, screening, treatment, and survival factors that impact disparities. This scope of work would not be feasible without the availability of six distinctive BWG models: Dana Farber (D), Erasmus (E), Georgetown- Einstein (GE), MD Anderson (M), Stanford (S) and Wisconsin-Harvard (W). The aims encompass multiple RFA priority areas, and we have set aside Rapid Response funds to address remaining priority areas, support cross-cancer CISNET collaborations, and foster junior career enhancement. Each aim includes three or more model groups selected for their unique structure and includes outside collaborators and junior investigators. The models will share common inputs and provide a standard set of outcomes for benefits (e.g., distant recurrences and deaths avoided, mortality reductions, distant disease-free survival, and life years and quality- adjusted life years), harms (e.g., false positives and benign biopsies, interval cancers, advanced stage diagnoses, overdiagnosis and treatment impact on quality of life), and costs. Continuously funded for the past 19 years, the modeling teams have published 204 research papers informing public health policy decisions and trained 13 junior investigators. For this proposal, the BWG will partner with the American Cancer Society, the American College of Radiology, the American Society of Clinical Oncology, the Breast Cancer Surveillance Consortium, and others. An experienced Coordinating Center provides the infrastructure to support the project goals including resource sharing and model accessibility. The exceptional environment provides unprecedented synergy and leveraging of resources to address new research questions and support career development that would not otherwise be possible. Overall, this research will advance modeling research and guide breast cancer control policy.