Tissue Systems Biology for Breast Cancer Prognostic and Predictive Testing

描述(申请人提供)：乳腺癌是女性最常被诊断的癌症类型，全世界每年有130万新诊断病例和465,000例死亡病例。迫切需要改进的预后和预测工具，以帮助乳腺癌的个体化治疗。特别需要进行检测，以确定需要积极治疗和监测的高风险患者，以及可能避免不必要的化疗的低风险患者，并选择个人可能对其有反应的特定治疗方法。这种测试对于改善疾病管理和乳腺癌患者的存活率至关重要。该项目的长期目标是开发一种基于组织的多重免疫荧光生物标记物检测乳腺癌并将其商业化，以比目前的诊断工具更高的敏感性和特异性来预测临床结果和对治疗的反应。一组最佳的生物标记物将使用组织系统来确定，这些组织系统可以在从回顾研究中构建的分类器的帮助下被简化为决定“指数”。在第一阶段，该项目的具体目标是通过对预后良好的患者和预后较差的患者的乳腺肿瘤组织微阵列进行多重免疫荧光染色，对一组24个预测和预测功能生物标记物进行回顾性评估。生物标志物的精确细胞内测量将通过对荧光数字成像病理产生的图像进行定量分析来进行。生物标记物的测量将与临床和病理数据相关联，以确定一组最佳的功能生物标记物。分类器软件将使用最佳生物标记物小组建立，以预测复发风险、存活率和临床结果。分类器将是将复杂的生物标记物数据转换为有意义的预后指标的关键解决方案。在该项目的第二阶段，该实用程序是对目前在诊断肿瘤组织切片上进行的IHC测量的补充。该测试的成功开发将为乳腺癌的个性化决策和改进疾病管理提供更准确的预测和预测。公共卫生相关性：迫切需要改进的预后和预测性测试，以帮助对乳腺癌进行个体化治疗。这项拟议的研究旨在开发一种组织系统生物学(CSBTM)图谱测试，该测试测量肿瘤的关键功能组合，包括控制肿瘤扩散的免疫系统和肿瘤对癌症治疗的反应。这项测试将使个别乳腺癌患者能够更准确地预测和预测治疗反应，以改善对疾病的管理。

DESCRIPTION (provided by applicant): Breast cancer is the most frequently diagnosed type of cancer in women, with 1.3 million new diagnoses and 465,000 deaths annually worldwide. There is an acute need for improved prognostic and predictive tools to aid individualized treatment for breast cancer. Tests are specifically required to identify high risk patients requiring aggressive therapy and monitoring, low risk patients who may be spared unnecessary chemotherapy, and to select specific therapies to which individuals are likely to respond. Such tests are critical to improve disease management and survival rates for breast cancer patients. The long term objective of the project is to develop and commercialize a tissue-based multiplexed immunofluorescence biomarker test for breast cancer to predict clinical outcome and responses to therapies with higher sensitivity and specificity than current diagnostic tools. An optimal panel of biomarkers will be determined using the Tissue Systeumors that can be reduced to decision "indices" with the aid of classifiers constructed from retrospective studies. In Phase I the project specifically aims to retrospectively evaluate a panel of 24 prognostic and predictive functional biomarkers by multiplexed immunofluorescence staining on tissue microarrays of breast tumor tissues from patients with good outcome and patients with poor outcome. Precise intracellular measurements of the biomarkers will be made by quantitative analysis of images generated by fluorescence digital imaging pathology. The biomarker measurements will be correlated with clinical and pathological data to determine an optimal panel of functional biomarkers. Classifier software will be built using the optimal biomarker panel to predict recurrence risk, survival and clinical outcome. The classifier will be the critical solution to convert the complex biomarker data to meaningful indices for prognostic purposes. In the Phase II of the project the utility, speciest as an addition to thecurrent IHC measurements performed at diagnosis tumor tissue sections. Successful development of the test will enable more accurate prognoses and predictions for individualized decision-making and improved disease management for breast cancer. PUBLIC HEALTH RELEVANCE: There is an acute need for improved prognostic and predictive tests to aid individualized management for breast cancer. The proposed research aims to develop a Tissue Systems Biology (CSBTM) profiling test that measures a combination of the key functions of tumors including, the immune system, that control tumor spread and the responses of tumors to cancer therapies. The test will enable more accurate prognoses and predictions of responses to therapies for individual breast cancer patients to improve management of the disease.