Benign Breast Registry to Assess Valid Endpoints

描述（由申请人提供）： 良性乳腺疾病（BBD）正在成为一个重要的诊断和治疗挑战。筛查性乳房X线摄影术的日益广泛使用使得临床上发现早期乳腺病变成为可能。流行病学研究提供了证据，良性乳腺病变和乳腺癌的后续风险之间的显着关系。前瞻性随机化学预防试验的结果为风险增加的妇女预防乳腺癌提供了新的药理学选择。对临床医生和患者的挑战源于良性乳腺疾病的异质性，以及缺乏可靠的标准来准确分配预后意义和确定活检结果的临床管理。看来，形态学和组织病理学的区别已经达到了极限。需要更新的、基于分子的测定来更严格和准确地定义风险类别。家庭风险评估计划（FRAP）是由玛丽戴利博士于1991年在福克斯蔡斯癌症中心（FCCC）建立的，目的是根据家族病史和/或良性乳腺疾病的个人病史，收集一组乳腺癌风险增加的家庭，以供研究。迄今为止，784名有活检证实的良性乳腺疾病个人病史的妇女参加了FRAP。戈德温博士是戴利博士的长期合作者，他已经开始了一系列结合激光捕获显微切割（LCM）和蛋白质组学方法的实验，以识别乳腺组织中的标记蛋白。这项合作提供了一个理想的机会，试点使用蛋白质组学，以确定新的标志物的乳腺癌风险在这一人群中。本项目的主要目的是探索LCM和蛋白质组学分析与BBD乳腺标本的应用，并验证这些蛋白质被发现过表达使用免疫组化方法与BBD标本FRAP参与者。第二个目的是将蛋白质组学标记物与传统的组织病理学定义相关联，并探索它们与其他临床和流行病学风险标记物的相关性。如果有希望，这项工作将导致一个更大的前瞻性临床研究项目，以验证试点研究的结果，并探索作用机制。

DESCRIPTION (provided by applicant): Benign breast disease (BBD) is emerging as an important diagnostic and therapeutic challenge. The increasingly widespread use of screening mammography has made it possible to detect early breast lesions clinically. Epidemiologic studies have provided evidence for a significant relationship between benign breast lesions and subsequent risk for breast cancer. And the results of prospective randomized chemoprevention trials have provided new pharmacologic options for breast cancer prevention to women at increased risk. The challenges to clinicians and their patients stem from the heterogeneous nature of benign breast disease and the lack of reliable criteria to accurately assign prognostic significance and determine clinical management for a biopsy finding. It appears that the limits of morphologic and histopathologic discrimination have been reached. Newer, molecular-based assays are needed to define risk categories with more rigor and accuracy. The Family Risk Assessment Program (FRAP) was established at the Fox Chase Cancer Center (FCCC) in 1991 by Dr. Mary Daly to assemble a cohort of families at increased risk for breast cancer based on family history of disease and/or personal history of benign breast disease for research purposes. To date, 784 women with a personal history of biopsy-proven benign breast disease are participating in FRAP. Dr. Godwin, a long time collaborator with Dr. Daly, has begun a series of experiments combining laser capture microdissection (LCM) and proteomic approaches to identify marker proteins in breast tissues. This collaboration provides an ideal opportunity to pilot the use of proteomics to identify novel markers of breast cancer risk in this population. The primary aims of this project are to explore the application of LCM and proteomic analyses to breast specimens with BBD and to validate those proteins found to be overexpressed using immunohistochemical approaches with BBD specimens from FRAP participants. A secondary aim is to correlate proteomic markers with traditional histopathologic definitions and to explore their correlation with other clinical and epidemiologic markers of risk. If promising, this work would lead to a larger prospective clinical research project to validate the findings of the pilot study and explore mechanisms of action.