Stromal MRI characteristics & gene expression profiles as predictors of outcome

描述（由申请人提供）：癌症相关基质在恶性肿瘤的进化过程中已经成为一个动态的伙伴。基因表达数据已经阐明了与特定生物学相关的功能特征，包括与基质相关的功能特征，并且最近被发现具有预后意义。我们已经开发了技术工具来量化乳腺ce - mri正常间质的百分比增强值。在我们之前发表的工作中，我们表明，在接受新辅助化疗的乳腺癌患者中，乳腺间质的平均整体增强值与无病生存相关。本研究表明，宿主乳腺组织具有MRI可测量的预后特性。我们进一步扩展了这些研究，以评估基质与肿瘤邻近程度的关系。在我们目前的初步数据中，我们发现在所有患者中，肿瘤周围的增强百分比随着距离的增加而减少，并且该区域在组织学上与血管生成的显著增加有关。我们假设，整体宿主组织特性和肿瘤附近的肿瘤相关基质对肿瘤生物学至关重要，并将影响局部晚期乳腺癌患者的预后。在本提案中，我们的主要终点将是研究CALGB 15007/ ACRIN 6657对比增强乳房MRI和相关科学研究（“ISPY”试验）中浸润性乳腺癌患者的MRI特征基质和基因表达阵列特征是否与无复发生存相关，以表征局部晚期乳腺癌新辅助治疗患者的肿瘤反应。

DESCRIPTION (provided by applicant): The cancer associate stroma has come to light as a dynamic partner in the evolution of malignancy. Gene expression data have elucidated functional signatures that are associated with specific biology, including that associated with stroma and have recently been found to have prognostic significance. We have developed the technical tools to quantify percent enhancement values in normal appearing stroma from CE-breast MRIs. In our previously published work, we showed that mean global enhancement values of the breast stroma were associated with disease-free survival in patients with breast cancer receiving neoadjuvant chemotherapy. This study revealed that host breast tissue had properties measurable by MRI that were prognostic. We extended these investigations further to evaluate the stroma in relationship to tumor proximity. In our current preliminary data, we found that in all patients, percent enhancement decreased from the periphery of the tumor with increasing distance, and that this region was histologically associated with significantly increased angiogenesis. We hypothesize that both global host tissue properties, and cancer- associated stroma, adjacent to the tumor, are critical to tumor biology and will be prognostic for outcomes in patients with locally advanced breast cancer. In this proposal, our primary endpoints will be to address whether MRI-characterized stroma and gene expression array signatures are associated with relapse free survival in patients with invasive breast cancer enrolled in the CALGB 15007/ ACRIN 6657 Contrast-Enhanced Breast MRI and Correlative Science Studies to Characterize Tumor Response in Patients Undergoing Neoadjuvant Treatment for Locally Advanced Breast Cancer ("ISPY" trial). PUBLIC HEALTH RELEVANCE: This project addresses the hypothesis that the host tissue and cancer-associated stroma have biologic properties that are prognostic and predictive of outcomes in breast cancer patients. Our strategy will be to apply the novel tools we have developed using MRI to a completed clinical trial that enrolled invasive breast cancer patients to receive neoadjuvant chemotherapy and undergo serial tumor biopsy and breast MRI, the CALGB 15007/ ACRIN 6657 Contrast-Enhanced Breast MRI and Correlative Science Studies to Characterize Tumor Response in Patients Undergoing Neoadjuvant Treatment for Locally Advanced Breast Cancer ("ISPY" trial). We will use pre-treatment MRIs to measure enhancement values globally and topographically for each patient. Quantitative measures will be associated recurrence free survival, and a multivariable regression model that accounts for other prognostic factors will be determined. Then, gene expression array data from the pre-treatment tumor biopsy will be analyzed for expression array signatures and their association with outcomes. Gene expression signatures with biologic function will also be investigated, and all signatures will be correlated with MRI phenotypes and outcome. These studies will allow us to validate whether stromal MRI measurements are prognostic, and to determine whether cancer- associated stromal gene expression signatures improve prediction of outcomes.