Advancing Evidence of the Associations between specific Benign Breast Diagnoses and Future Breast Cancer Risk

项目总结 这个项目的长期目标是了解特定的良性乳腺疾病之间的关系 (BBD)诊断和未来乳腺癌风险，并利用这一知识更好地识别处于 乳腺癌的高风险，可能受益于更密集的一级和/或二级预防战略。 BBD是一种常见的乳腺活检发现，包括各种不同的诊断，包括 乳腺组织的正常变异到具有或不具有非典型特征的增生性改变。女性与某些人 众所周知，BBD的诊断具有发展为浸润性乳腺癌的高风险，风险因以下因素而异 良性病变内有癌变特征的组织学异常程度。对风险的估计有 主要是对已知高危类别内的BBD诊断进行量化。这在生物学上是可信的 其他BBD诊断也可能表现为乳腺癌的不同危险因素，并改善风险预测。 然而，与许多特定的BBD诊断相关的癌症风险尚未得到广泛研究， 尽管通过筛查乳房X光检查发现BBD的发病率不断上升。此外，协会 BBD诊断与癌症风险之间的关系可能会因绝经状态或确诊后的时间而改变。 了解与特定的BBD诊断和聚集相关的乳腺癌风险的大小 具有相似风险的诊断有可能为当前的乳腺病理实践提供信息，改进风险预测 模型，并为制定个性化的预防战略提供证据。这样做的目的是 建议表征浸润性乳腺癌和导管原位癌相关的未来风险 特殊的BBD诊断通常合并为两大类非增殖性病变和 无异型性的增生性病变，并确定具有相似风险的特定诊断群(目标1)。 此外，我们将确定这些相关性是否因绝经状态或自BBD诊断(AIM)以来的时间而不同 2)。该应用程序利用了乳腺癌监测联盟的独特研究资源， 包括具有风险预测建模和基于风险的专业知识的多学科导师团队 筛查、生物统计学、癌症流行病学、医学和病理学。 这些目标将提供对BBD诊断与未来乳腺癌关系的重要理解。 风险。此外，我们的工作还将为当前乳腺病理学的临床实践和改进后的发展提供参考。 风险预测模型，识别具有类似风险的病变。这方面的跨学科培训环境 建议书将为申请者提供获得技术技能、建立研究能力、 额外的教育培训，并发展内容领域的专业知识，以促进她的职业生涯作为未来 独立研究人员。

PROJECT SUMMARY The long-term goal of this project is to understand the relationship between specific benign breast disease (BBD) diagnoses and future breast cancer risk, and to use this knowledge to better identify groups of women at high risk of breast cancer that may benefit from more intensive primary and/or secondary prevention strategies. BBD is a common breast biopsy finding and encompasses a diverse spectrum of diagnoses ranging from normal variations in breast tissue to proliferative changes with or without atypical features. Women with certain BBD diagnoses are known to have a high risk for development of invasive breast cancer, with risk varying by degree of histological abnormality with cancerous-like features within the benign lesion. Estimates of risk have primarily been quantified for BBD diagnoses within known high-risk categories. It is biologically plausible that other BBD diagnoses may also manifest as distinct risk factors for breast cancer and improve risk prediction. However, the risks of cancer associated with many specific BBD diagnoses have not been extensively studied, despite an increasing incidence of BBD detected by screening mammography. Moreover, associations between BBD diagnoses and cancer risk may be modified by menopausal status or time since diagnosis. Understanding the magnitude of breast cancer risk associated with specific BBD diagnoses and clustering diagnoses with similar risk has the potential to inform current breast pathology practice, improve risk prediction models, and provide evidence for the development of personalized prevention strategies. The objective of this proposal is to characterize the future risk of invasive breast cancer and ductal carcinoma in situ associated with specific BBD diagnoses typically combined into two broad categories of non-proliferative lesions and proliferative lesions without atypia, and to identify clusters of specific diagnoses with similar risk (Aim 1). Further, we will determine if these associations differ by menopausal status or time since BBD diagnosis (Aim 2). This application leverages the unique research resources of the Breast Cancer Surveillance Consortium, including a multidisciplinary team of mentors with expertise in risk prediction modeling and risk-based screening, biostatistics, cancer epidemiology, medicine, and pathology. These aims will provide a critical understanding of the relationship of BBD diagnoses with future breast cancer risk. Moreover, our work will inform current breast pathology clinical practice and the development of improved risk prediction models, identifying lesions with similar risk. The interdisciplinary training environment for this proposal will provide the applicant the opportunity to gain technical skills, build research competency, undergo additional educational training, and develop content area expertise to further her career as a future independent researcher.