Benign Breast Registry to Assess Valid Endpoints

描述(由申请人提供)： 良性乳腺疾病(BBD)正成为诊断和治疗的一个重要挑战。筛查乳房X光检查的日益广泛的使用使临床发现早期乳腺病变成为可能。流行病学研究已经为良性乳腺病变和随后的乳腺癌风险之间的显著关系提供了证据。前瞻性随机化学预防试验的结果为高风险女性预防乳腺癌提供了新的药理学选择。临床医生和他们的患者面临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处理。似乎已经达到了形态和组织病理学歧视的极限。需要更新的、基于分子的分析来更严格、更准确地定义风险类别。家庭风险评估计划(FRAP)由Mary Daly博士于1991年在福克斯·蔡斯癌症中心(Fccc)建立，旨在根据家族病史和/或良性乳腺疾病个人病史收集乳腺癌风险增加的家庭队列，用于研究目的。到目前为止，784名有活检证实的良性乳腺疾病个人病史的妇女正在参加FRAP。戈德温博士是戴利博士的长期合作伙伴，他已经开始了一系列实验，将激光捕获显微解剖(LCM)和蛋白质组学方法结合起来，以识别乳房组织中的标记蛋白。这一合作提供了一个理想的机会来试验使用蛋白质组学来确定这一人群中乳腺癌风险的新标记。这个项目的主要目的是探索LCM和蛋白质组学分析在患有BBD的乳房标本中的应用，并用来自FRAP参与者的BBD样本用免疫组织化学方法验证那些过度表达的蛋白质。第二个目标是将蛋白质组标记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的相关性。如果前景看好，这项工作将导致一个更大的前瞻性临床研究项目，以验证先导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.