Abstract Purpose: Risk-reducing breast surgery (RRBS) is an established preventive strategy for women at high genetic or familial risk of breast cancer. Histopathological evaluation of RRBS specimens may reveal incidental findings (IFs), including occult malignancies and precursor lesions, but their prevalence and predictors remain insufficiently described. This study aimed to estimate the prevalence of IFs and identify associated risk factors in a Brazilian cohort. Methods: We conducted a cross-sectional analysis of 154 women who underwent RRBS at a tertiary public cancer center in Brazil between 2013 and 2025. Eligible patients carried pathogenic/likely pathogenic germline variants and/or fulfilled NCCN high-risk criteria. Histopathological assessment followed an institutional protocol with extensive tissue sampling. Logistic regression models evaluated demographic, clinical, and surgical predictors of IFs. Results: IFs were identified in 35% (54/154) of patients, including atypical proliferations (70%), DCIS (22%), and invasive neoplasia (8%). On multivariate analysis, older age (OR 1.071) and bilateral mastectomy (OR 3.27) were significant independent predictors of IFs. For invasive and DCIS findings, age was the only significant factor (OR 1.069). Genetic status showed no significant association. Conclusion: This study reports the highest prevalence of IFs in RRBS specimens to date, largely attributable to the comprehensive sampling protocol. Associations with clinical characteristics, particularly age, contrast with the absence of correlation between negative genetic testing and reduced risk. These findings highlight the importance of integrating detailed clinical and familial risk assessment into surgical decision-making, especially in resource-limited systems with restricted access to genetic testing. Citation Format: T. Fernandes, D. Silva, A. O. Magalhaes, B. Duarte, A. cabello, S. Ramalho, L. R. da Silva, G. Paiva, r. torresan, F. Brenelli, M. Minari, T. Gaspar, A. Viaro, S. Teixeira, M. Faucz, C. Alem, C. Cabello. Incidental Histopathological Findings in Risk Reducing Breast Surgery: A Cross Sectional Study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-02-14.
Fernandes et al. (Tue,) studied this question.