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.