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

项目总结 风险分层乳腺癌筛查策略是从一刀切筛查的范式转变 接近。以前的基于年龄的筛查策略被证明对特定的高危人群不利 人群，特别是BRCA1和BRCA2突变携带者和非洲血统的高危个体 侵袭性年轻发病间歇期乳腺癌。有一种尚未得到满足的临床需求，即确定哪些女性处于 侵袭性间歇性乳腺癌的高风险，如果没有严密的监测，结果会更差。 自加入根据风险衡量(智慧)进行筛查的妇女研究以来(Clinicaltrials.gov： NCT02620852)2020年，UChicago网站有1691名参与者；白人64.7%，黑人23.5%，6.8% 西班牙裔，因为我们位于芝加哥南部，而且在芝加哥的招聘工作非常有效 有色人种社区。越来越多的研究已经证明了诊断的等价性 将MRI缩写为完整的MRI协议。我们启动了芝加哥替代预防研究 对于乳腺癌(CAPSBRACA；Clinicaltrials.gov：NCT00989638)作为P20乳腺癌差异孢子 人口科学项目，以测试最先进的基因组测试，以识别妇女在 增加的风险，结合最先进的核磁共振技术，可以有效地检测和降级 侵袭性间歇性乳腺癌，并为高危女性提供个性化的管理方法 在不同的人群中。在我们的单一机构，130名基因定义的高风险参与者(平均年龄42岁) SD+12)，其中包括44个BRCA1，42个BRCA2，7个PALB2和25个PRS&GT；30%，这表明 在实践中，常见的基因变异可以识别出极高风险的女性。我们已经演示了 我们方法的可行性和拟议的研究将测试它在临床上的有效性、适应性和可伸缩性。 利用智慧平台优化对高危妇女的全面监测计划。我们的整体 目标是扩大到加利福尼亚州的另外三个地点，以扩大研究地点和参与者的多样性。 具体目标是：1)实施一年两次的简化磁共振成像，包括超快-DCE-MRI， 多中心标准化；改进和扩展我们的高风险两年一次的简化协议以实现快速，同时 临床准确性和跨影像设备的通用性；2)执行相关的科学和定量 分析MRI图像并建立可传播到其他中心的分析包；以及3)开发 并使用UF DCE-MRI评估自我监督深度学习(SSL)方法，以实现快速和准确 乳腺癌风险的计算生物标记物。CAPSBRACA将创新的基因组学和成像 来自实验室的有意义的临床干预研究，并有可能解决未满足的问题 在突变携带者中早期准确检测侵袭性年轻乳腺癌的临床需要。它 将影响美国每年近10,000名被诊断为有症状的乳腺癌的未经筛查的女性 40岁以下，以及数千名接受筛查的妇女患有侵袭性间歇性癌症的风险很高。

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.