Comparative Modeling of Precision Breast Cancer Control Across the Translational Continuum

摘要 CISNET乳腺工作组（BWG）提出了创新的建模研究，重点是新的精度 肿瘤学范例，有望重新定义乳腺癌控制的最佳实践。我们选择 重要的主题，其中建模适合填补证据空白，促进临床和政策翻译。 我们的方法的独特组成部分包括建模的绝对风险的疾病占多种风险 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志物的筛查方法，提供有关 精确的系统治疗及其对幸存者生活质量的影响，并调查种族差异。 具体目标是：1）评估新的精确筛选方法的影响; 2）评估 精确治疗模式在辅助、新辅助和转移性环境中的影响; 3） 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 降低死亡率;以及4）提供证据，指导干预措施，通过量化 影响差异的多种风险、筛查、治疗和生存因素。这一工作范围将不会 可行的没有六个独特的BWG模型的可用性：达纳法伯（D），伊拉斯谟（E），乔治敦- 爱因斯坦（GE）、MD安德森（M）、斯坦福大学（S）和威斯康星-哈佛大学（W）。目标包括多种RFA 我们已拨出快速反应资金，以解决剩余的优先领域， 跨癌症CISNET合作，并促进初级职业发展。每个目标包括三个或更多 根据其独特的结构选择了示范小组，其中包括外部合作者和初级调查员。 这些模型将共享共同的投入，并提供一套标准的效益结果（例如，遥远 避免的复发和死亡、死亡率降低、无远处疾病生存率、生命年和质量- 调整生命年），危害（例如，假阳性和良性活检，间隔癌，晚期 诊断，过度诊断和治疗对生活质量的影响）和成本。过去持续供资 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提供信息， 培训了13名初级调查员。对于这项提案，BWG将与美国癌症协会合作， 美国放射学会、美国临床肿瘤学会、乳腺癌监测 财团等。一个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。特殊的环境提供了 前所未有的协同作用和资源利用，以解决新的研究问题和支持职业生涯 否则不可能实现的发展。总的来说，这项研究将推动建模研究， 指导乳腺癌控制政策。

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.