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: 10459788
• 负责人: Jennifer M. Yeh
• 金额: $ 75.55万
• 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/10459788
• 关键词: Address; Adolescent; Advisory Committees; 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; Dose; Early Diagnosis; Economics; Elements; Estrogen receptor positive; Exposure to; Face; Female; Goals; Guidelines; High Risk Woman; Incidence; Internal Medicine; Intervention; Knowledge; Late Effects; Lead; 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; Preventive service; 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; Societies; Survivors; Tamoxifen; United States National Academy of Sciences; 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.

项目总结/摘要 儿童和青少年癌症幸存者（“幸存者”）面临早期死亡和治疗的高风险- 相关的晚期影响，包括随后的乳腺癌。大约30%的女性幸存者以前 接受胸部放射治疗的人在50岁之前会患上乳腺癌，这种风险与BRCA 1突变携带者相似。 儿童肿瘤学小组建议早期筛查乳腺癌（在那些接受过 在25岁时开始接受放射治疗，但<15%的幸存者坚持治疗，许多是因为经济障碍。风险- 减少药物，如选择性雌激素受体调节剂和芳香酶抑制剂， 一些幸存者完全避免乳腺癌（与早期发现筛查和治疗相比），因为这些 药物可将雌激素受体阳性（ER+）肿瘤的风险降低50%， 美国预防服务工作队的妇女。然而，降低风险的药物目前还没有 为高危幸存者提供标准护理，不仅包括那些以前接受过放射治疗的幸存者， 新出现的数据，那些谁暴露于高剂量的蒽环类药物化疗。童年的稀有 青少年癌症和捕获后续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优先领域，我们建议使用模拟 建模和纵向观察数据，通过评估临床受益为临床护理提供信息， 降低风险的药物对儿童和青少年癌症幸存者的危害。我们将建立在我们的 与癌症干预和监测建模网络（CISNET）建立了合作关系， 儿童癌症幸存者研究（CCSS）和圣裘德终身队列研究：（1）完善两个CISNET 反映幸存者对乳腺癌风险、筛查和预防的现有知识的模型;（2） 以易于访问的在线查找表的形式提供模型结果，避乳 癌症），危害（例如，药物副作用）以及增加风险和减少风险给妇女和社会带来的成本 药物使用5年筛选;和（3）进行探索性分析，以评估风险的影响- 减少药物治疗和按种族进行结果筛查。我们提出的研究将有很大的潜力， 以降低乳腺癌风险的药物为例，重塑当前的生存护理模式 了解如何将预防剂纳入当前的生存建议， 实践这项工作还将提供一个框架，阐明关键要素和干预点， 引导努力尽量缩小差距。该项目在概念上具有创新性，在临床上具有重要意义， 同时考虑已证明有效的初级预防癌症药物和筛查 建议.这项工作将通过提供数据为临床护理指南提供信息， 创建幸存者和护理提供者可以用来指导乳腺癌护理讨论的资源 预防和早期发现。