Can risk-reducing medications improve breast cancer prevention in childhood and adolescent cancer survivors? Comparative modeling to inform care

降低风险的药物可以改善儿童和青少年癌症幸存者的乳腺癌预防吗？

• 批准号: 10675772
• 负责人: Jennifer M. Yeh
• 金额: $ 64.4万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10675772
• 关键词: Address; Adolescent; Affordable Care Act; Age; Anthracycline; Area; Aromatase Inhibitors; BRCA1 Mutation; Black race; Breast; Breast Cancer Detection; Breast Cancer Early Detection; Breast Cancer Prevention; Breast Cancer Risk Factor; Cancer Intervention and Surveillance Modeling Network; Cancer Survivor; Caring; Cessation of life; Chest; Childhood; Childhood Cancer Survivor Study; Clinical; Clinical Course of Disease; Cohort Studies; Collaborations; Combination Medication; Communities; Data; Decision Aid; Decision Modeling; Development; Disparity; Dose; Early Diagnosis; Economics; Elements; Estrogen receptor positive; Exposure to; Face; Female; Goals; Guidelines; High Risk Woman; Incidence; Internal Medicine; Intervention; Knowledge; Late Effects; Magnetic Resonance Imaging; Malignant Neoplasms; Mammography; Medicine; Methodology; Modality; Modeling; Morbidity - disease rate; Outcome; Pediatric Oncology Group; Performance; Pharmaceutical Preparations; Postmenopause; Prevention; Prevention trial; Preventive; Primary Cancer Prevention; Primary Prevention; Publishing; Quality of life; Race; Radiation; Recommendation; Regimen; Research; Resources; Risk; Risk Reduction; Saint Jude Children' s Research Hospital; Selective Estrogen Receptor Modulators; Shapes; Societies; Survivors; Tamoxifen; United States National Academy of Sciences; United States Preventative Services Task Force; Woman; Work; barrier to care; care providers; chemotherapy; childhood cancer survivor; clinical care; clinically relevant; comparative; cost; follow-up; high risk; improved; innovation; malignant breast neoplasm; models and simulation; mortality; mortality disparity; mortality risk; mutation carrier; network models; prospective; routine screening; screening; screening guidelines; shared decision making; side effect; standard care; survivorship; tumor; uptake; web site

PROJECT SUMMARY/ABSTRACT Survivors of childhood and adolescent cancer (“survivors”) face high risks for early mortality and treatment- related late effects, including subsequent breast cancer. Approximately 30% of female survivors previously treated with chest radiation will develop breast cancer before age 50, a risk similar to BRCA1 mutation carriers. The Children’s Oncology Group recommends early screening for breast cancer (in those who received radiation) starting at age 25, but <15% of survivors are adherent, many because of economic barriers. Risk- reducing medications, such as selective estrogen receptor modulators and aromatase inhibitors, could allow some survivors to avoid breast cancer entirely (vs. early detection with screening and treatment) since these drugs reduce the risk of estrogen receptor positive (ER+) tumors by 50% and are recommended for high-risk women by the U.S. Preventive Services Task Force. However, risk-reducing medications are not currently standard care for high-risk survivors which includes not only those previously treated with radiation but given emerging data, those who were exposed to high doses of anthracycline chemotherapy. The rarity of childhood and adolescent cancer and the long latency needed to capture subsequent cancers limit the feasibility of prospective prevention trials. Addressing all RFA-CA-20-027 priority areas, we propose to use simulation modeling and longitudinal observational data to inform clinical care by evaluating the clinical benefits and harms of risk-reducing medications among childhood and adolescent cancer survivors. We will build on our established collaboration with the Cancer Intervention and Surveillance Modeling Network (CISNET), the Childhood Cancer Survivor Study (CCSS) and the St. Jude Lifetime Cohort Study to: (1) refine two CISNET models to reflect current knowledge on breast cancer risk, screening and prevention among survivors; (2) provide model results in readily accessible online look-up tables summarizing benefits (e.g., avoiding breast cancer), harms (e.g., medication side effects) and costs to women and society of adding risk-reducing medication use for 5 years to screening; and (3) conduct exploratory analyses to assess the impact of risk- reducing medications and screening on outcomes by race. Our proposed research will have high potential to reshape current paradigms for survivorship care, using breast cancer risk-reducing medications as an example for understanding how preventive agents can be incorporated into current survivorship recommendations and practice. This work will also provide a framework to illuminate key elements and intervention points that can guide efforts to minimize disparities. This project is conceptually innovative and clinically important by simultaneously considering proven effective primary cancer prevention medicines together with screening recommendations. This work will be highly translational by providing data to inform clinical care guidelines and create resources that survivors and care-providers can use to guide care discussions on breast cancer prevention and early detection.

项目摘要/摘要 儿童期和青少年癌症（“幸存者”）的幸存者面临早期死亡率和治疗的高风险 - 相关的后期作用，包括随后的乳腺癌。以前约有30％的女性存活率 用胸部辐射治疗将在50岁之前患上乳腺癌，这种风险类似于BRCA1突变载体。 儿童肿瘤学小组建议对乳腺癌进行早期筛查（在那些接受的人中 从25岁开始的辐射），但<15％的生存是遵守的，其中许多是由于经济障碍。风险- 减少药物，例如选择性雌激素受体调节剂和芳香酶抑制剂，可以允许 一些生存是为了完全避免乳腺癌（与筛查和治疗的早期检测），因为 药物将雌激素受体阳性（ER+）肿瘤的风险降低50％，建议用于高危 美国预防服务工作队的妇女。但是，目前尚未降低风险的药物 高风险幸存者的标准护理，不仅包括先前接受辐射治疗的人，而且包括 新兴数据，那些暴露于高剂量的蒽环类化疗的数据。童年的稀有性 和青春期癌症以及捕获随后的癌症所需的长潜伏期限制了 前瞻性预防试验。解决所有RFA-CA-20-027优先区域，我们建议使用仿真 建模和纵向观察数据，通过评估临床益处和 儿童和青少年癌症生存中降低风险的药物的危害。我们将在我们的基础上建立 与癌症干预和监视建模网络（CISNET）建立了合作， 儿童癌症幸存者研究（CCSS）和圣裘德寿命队列研究 模型以反映有关乳腺癌风险，筛查和预防的当前知识的模型； （2） 提供模型结果，以易于访问的在线查找表总结收益（例如，避免乳房） 癌症），危害（例如，药物副作用）以及妇女的成本以及增加风险的社会 用药5年以筛查； （3）进行探索性分析以评估风险的影响 - 减少药物并筛查种族结果。我们拟议的研究将具有很高的潜力 以减少乳腺癌风险的药物为例，重塑当前生存护理范式用于生存护理 为了了解如何将预防剂纳入当前的生存建议和 实践。这项工作还将提供一个框架，以阐明关键要素和干预点可以 指导努力以最大程度地减少分布。该项目在概念上是创新的，并且在临床上很重要 同时考虑有效的有效原发性癌症预防药物以及筛查 建议。通过提供数据来告知临床护理指南和 创建幸存者和护理人员可以用来指导乳腺癌的护理讨论的资源 预防和早期检测。