Predicting Breast Cancer Risk after Benign Percutaneous Biopsy

项目摘要 在美国，每年有超过100万女性接受良性乳腺疾病（BBD）的活检诊断， 这就迫切需要为这些妇女开发风险预测工具。父母补助金涉及 该补充旨在通过评估自我报告的因素来改善BBD女性的风险预测， 乳腺摄影密度和组织生物标志物。背景年龄相关性小叶退化（ALI）的评价 小裂片是该项目的核心组成部分，因为这些结构给大多数BC前体带来风险。妊娠 降低长期乳腺癌风险，但增加风险短暂>20年，这是为了反映 组织重塑和巨噬细胞浸润，伴随产后复旧（PPI）。我们的家长grant 侧重于评估ALI作为风险标志物，但无法充分识别与PPI相关的风险生物标志物 因为大多数活组织检查都是在孩子出生多年后进行的。PPI以大量凋亡为特征 上皮细胞，巨噬细胞内流和γH2AX（DNA损伤标志物）表达增加。我们 假设PABC风险因素，如母乳喂养失败、肥胖和非裔美国人种族， 在怀孕后收集的正常组织中的免疫细胞组成， 患上“慢性乳腺病”会增加患乳腺癌的风险。我们将通过分析来测试这一提议。 免疫细胞组成和γH2AX在“正常”乳腺组织捐赠的科门组织库中， 在活产后10年内收集经产和匹配的未经产AA和高加索女性。 了解多年来收集的乳腺组织中炎症和DNA损伤的决定因素 怀孕后可以提供所需的见解，以推进风险预测和预防，特别是 早期致命癌症这个项目提供了一个很好的机会，发展博士Ogony的专业知识， 一个跨学科的研究人员，专注于乳腺癌的种族差异。指导和资源， 马约为这项研究和相关培训提供了极好的支持。

Project Summary More than one million women receive biopsy diagnoses of benign breast disease (BBD) in the U.S. each year, which creates an important need to develop risk prediction tools for these women. The parent grant related to this supplement seeks to improve risk prediction for women with BBD by assessing self-reported factors, mammographic density and tissue biomarkers. Evaluation of age-related lobular involution (ALI) of background lobules is a central component of the project, as these structures give risk to most BC precursors. Pregnancy reduces long-term breast cancer risk, but increases risk transiently for >20 years, which is proposed to reflect tissue remodeling and macrophage infiltration which accompany postpartum involution (PPI). Our parent grant focuses on assessment of ALI as a risk marker, but cannot adequately identify risk biomarkers related to PPI because most biopsies were performed many years post-childbirth. PPI is characterized by massive apoptosis of epithelial cells, macrophage influx, and increased expression of γH2AX, a marker of DNA damage. We hypothesize that risk factors for PABC, such as failure to breastfeed, obesity and African American race, affect immune cell composition in normal tissues collected in the period following pregnancy and that some women develop a “chronic mastopathy” that increases breast cancer risk. We will test this proposal by analyzing immune cell composition and γH2AX in “normal” breast tissues donated in the Komen Tissue Bank among parous and matched nulliparous AA and Caucasian women collected within 10 years of a live birth. Understanding the determinants of inflammation and DNA damage in breast tissues collected in the years following pregnancy could provide insights required to advance risk prediction and prevention, particularly for early onset lethal cancers. This project provides an excellent opportunity to develop Dr. Ogony’s expertise as an inter-disciplinary researcher focusing on racial disparities in breast cancer. Mentorship and resources at Mayo provide excellent support for this research and related training.