Chicago Alternative Prevention Study for BReast CAncer in Diverse Populations of High-Risk Women (CAPSBRACA)

芝加哥不同高危女性人群乳腺癌替代预防研究 (CAPSBRACA)

• 批准号: 10737279
• 负责人: Hiroyuki Abe
• 金额: $ 126.82万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-11 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10737279
• 关键词: Abbreviations; Address; Adherence; Affect; African ancestry; Age; Age Years; American College of Radiology; BRCA1 Mutation; BRCA1 gene; BRCA2 Mutation; BRCA2 gene; Benign; Biological Markers; Black race; Breast; Breast Cancer Detection; Breast Cancer Risk Factor; COVID-19 pandemic; California; Cancer Detection; Chicago; Clinic; Clinical; Clinical Trials; Clinical effectiveness; Collaborations; Color; Communities; Contralateral; Data; Detection; Diagnosis; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Drug Kinetics; Early Diagnosis; Enrollment; Evaluation; Family history of; Funding; Future; Genetic; Genetic Risk; Genomics; Germ-Line Mutation; High Risk Woman; Hispanic; Hospitals; Image; Individual; Influentials; Inherited; Institution; Intervention; Ipsilateral; Kinetics; Label; Laboratory Research; Lesion; Location; Longitudinal cohort; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of ovary; Mammographic screening; Measurement; Measures; Methods; Modeling; Outcome; Output; PALB2 gene; Participant; Performance; Population; Population Heterogeneity; Population Sciences; Predisposition; Prevention; Protocols documentation; Recommendation; Research Design; Resources; Risk; Risk Factors; Risk Management; Science; Side; Site; Standardization; Surveillance Program; Techniques; Testing; Tissues; Training; Translating; United States Preventative Services Task Force; Validation; Vascular blood supply; Woman; Work; breast cancer survival; cancer health disparity; cancer invasiveness; cancer risk; deep learning; deep learning model; disparity reduction; efficacy evaluation; experience; genetic testing; genetic variant; high risk; high risk population; imaging facilities; imaging modality; improved; innovation; learning strategy; malignant breast neoplasm; model building; mutation carrier; novel; personalized approach; pragmatic study; premature; primary care setting; quality assurance; radiologist; recruit; risk prediction model; risk stratification; screening; standard of care; young woman

PROJECT SUMMARY Risk-stratified breast cancer screening strategies are a paradigm shift from the one-size-fits-all screening approach. Previous age-based screening strategies proved to be disadvantageous to specific high-risk populations, particularly BRCA1 and BRCA2 mutation carriers and individuals of African ancestry at high risk for aggressive young onset interval breast cancers. There is an unmet clinical need to identify women who are at high risk of aggressive interval breast cancer that would have a poorer outcome without intensive surveillance. Since joining the Women informed to screen based on measures of risk (Wisdom) Study (clinicaltrials.gov: NCT02620852) in 2020, the UChicago site has enrolled 1691 participants; 64.7% White, 23.5% Black and 6.8% Hispanic because of our location on the south side of Chicago and highly effective recruitment efforts in communities of Color. A growing number of studies have demonstrated the diagnostic equivalency of abbreviated MRI to the full MRI protocol. We launched the Chicago Alternative Prevention Study for BReast CAncer (CAPSBRACA; clinicaltrials.gov:NCT00989638) as a P20 Breast Cancer Disparities SPORE population science project to test the hypothesis that state-of-the-art genomic testing to identify women at increased risk, combined with state-of-the-art MRI techniques, could effectively detect and downstage aggressive interval breast cancers, and provide a personalized approach for management of high-risk women in diverse populations. At our single Institution, 130 genomically defined high-risk participants (mean age 42 SD+12) have been enrolled including 44 BRCA1, 42 BRCA2, 7 PALB2 and 25 with PRS >30%, suggesting common genetic variants can identify extremely high-risk women in practice. We have demonstrated the feasibility of our approach and the proposed study will test that it is clinically effective, adaptable, and can scale to optimize a comprehensive surveillance program for high-risk women using the Wisdom platform. Our overall objective is to expand to three additional sites in California to broaden the diversity of study sites and participants. The specific aims are to: 1) Implement biannual abbreviated MRI that includes ultrafast- DCE-MRI, with multicenter standardization; refine and expand our high-risk biannual abbreviated protocol to be fast, while both clinically accurate and generalizable across imaging facilities; 2) perform correlative science and quantitative analysis of MRI images and build an analysis package that can be disseminated to other centers; and 3) Develop and evaluate self-supervised deep learning (SSL) methods using UF DCE-MRI to enable fast and accurate computational biomarkers of breast cancer risk. CAPSBRACA translates innovative genomics and imaging research from the laboratory into meaningful clinical interventions and has the potential to address an unmet clinical need for early and accurate detection of aggressive young-onset breast cancers in mutation carriers. It will impact the nearly 10,000 unscreened women in the US diagnosed each year with symptomatic breast cancer under 40 years of age, and the thousands of screened women at high risk of aggressive interval cancers.

项目摘要 风险分层的乳腺癌筛查策略是从一刀切的筛查模式的转变 approach.以前的基于年龄的筛查策略被证明是不利的特定的高风险 人群，特别是BRCA 1和BRCA 2突变携带者和非洲血统的高风险个体， 侵袭性年轻发病间隔期乳腺癌。有一个未满足的临床需要，以确定妇女谁是在 侵袭性间隔期乳腺癌的高风险，如果不加强监测，结果会更差。 自从加入妇女知情筛选基于风险的措施（智慧）研究（clinicaltrials.gov： NCT 02620852），2020年，芝加哥大学研究中心共招募了1691名参与者; 64.7%为白色，23.5%为黑人，6.8%为 西班牙裔，因为我们在芝加哥南部的位置和高效的招聘工作， 颜色的社区。越来越多的研究表明， 将MRI简化为完整的MRI方案。我们启动了芝加哥替代预防研究 BReast CAncer（CAPSBRACA; clinicaltrials.gov：NCT 00989638）作为P20乳腺癌差异孢子 人口科学项目，以测试假设，国家的最先进的基因组测试，以确定妇女在 增加的风险，结合最先进的MRI技术，可以有效地检测和前期 侵袭性间隔期乳腺癌，并为高危女性的管理提供个性化的方法 在不同的人群中。在我们的单一机构，130名基因组定义的高风险参与者（平均年龄42岁）， SD+12），包括44例BRCA 1、42例BRCA 2、7例PALB 2和25例PRS > 30%，提示 在实践中，常见的遗传变异可以识别出极高风险的妇女。我们已经展示了 我们的方法的可行性和拟议的研究将测试它是临床有效的，适应性强，可以规模化 利用Wisdom平台优化针对高危女性的综合监测方案。我们的整体 目标是扩展到加州的另外三个研究中心，以扩大研究中心和参与者的多样性。 具体目标是：1）实施一年两次的简化MRI，包括超快- DCE-MRI， 多中心标准化;完善和扩展我们的高风险一年两次的简短协议，以快速，而这两个 临床上准确，可在成像设施中推广; 2）进行相关科学和定量 分析MRI图像，并建立一个可以传播到其他中心的分析包;以及3）开发 并使用UF DCE-MRI评估自监督深度学习（SSL）方法，以实现快速准确的 乳腺癌风险的计算生物标志物。CAPSBRACA将创新的基因组学和成像技术 从实验室研究到有意义的临床干预措施，并有可能解决未得到满足的 临床上需要对突变携带者中的侵袭性乳腺癌进行早期和准确的检测。它 将影响美国每年近10，000名未经筛查的女性被诊断为有症状的乳腺癌 40岁以下，以及数千名接受筛查的妇女，她们有患侵袭性间隔期癌症的高风险。