Abstract Background: Current breast cancer (BCa) screening guidelines do not adequately address transgender populations, despite known differences in hormone exposure and post-operative anatomy between transgender and cisgender patients of the same gender. The effects of gender-affirming hormone therapy (HT) and surgical intervention (SX) on BCa risk in transgender individuals remain poorly understood. Objective: To evaluate the incidence and predictors of BCa in transgender men and women, stratified by gender-affirming interventions (HT and SX). Methods: Using TriNetX (TriNetX, Inc., Cambridge, MA, United States), a de-identified health research network, we identified adults with a diagnosis of Gender Identity Disorder (GID) (ICD-10: F64.x) from 2003-2023. Patients were divided by sex assigned at birth and categorized into cohorts based on gender-affirming intervention: no intervention (NI), HT alone (≥1 year), and HT with SX. SX was limited to top surgeries, such as breast contouring and mastectomies. Patients with a past history of BCa, bottom surgery, or inconsistent medical timelines were excluded. The primary outcome was a diagnosis of malignant neoplasm of the breast (ICD-10: C50.x), recorded in at least two instances. Logistic regression was used to identify predictors of BCa risk. Results: Among 33,775 transgender women (assigned male at birth), 12 (0.036%) were diagnosed with BCa. Of these, 83.3% had no intervention, 16.7% received HT, and none received both HT and SX. HT alone was not associated with increased risk of developing BCa. Independent predictors of BCa included age at GID diagnosis (OR =d 1.07 per year, 95% CI: 1.05-1.09, p 0.001) and Black race (OR = 2.71, 95% CI: 1.13-5.76, p = 0.015). Among 44,117 transgender men (assigned female at birth), 37 (0.084%) were diagnosed with BCa. Most cases occurred in those with no intervention (72.9%), followed by HT+SX (21.6%), and HT alone (5.4%). Hormone therapy alone was not associated with increased risk. Individuals who received both HT and SX had significantly higher BCa prevalence compared to those with HT alone (0.25% vs. 0.07%, p = 0.01). Multivariate analysis showed increased odds of BCa with combined HT and SX (OR = 3.62, 95% CI: 1.02-10.14, p = 0.024), Black race (OR = 3.35, 95% CI: 1.20-8.15, p = 0.012), and age at GID diagnosis (OR = 1.07 per year, 95% CI: 1.05-1.09, p 0.001). Conclusion: This is the largest cohort study to date assessing BCa risk among transgender patients, and the first study to stratify risk by level of gender-affirming intervention. HT alone does not appear to increase BCa risk in transgender individuals. However, among transgender men, the combination of HT and SX was associated with significantly elevated risk. These findings may reflect differences in tissue preservation during mastectomy, lower screening rates, or increased pathological surveillance post-surgery. Black race and age at GID diagnosis were also associated with greater risk among both trans men and women. Our findings underscore the need for revised BCa screening guidelines that reflect the unique risk profiles of transgender populations and address intersectional disparities in care. Citation Format: D. Gilbert, A. Thakur, T. Tabernacki, M. Loria, M. A. Mart, S. Rhodes, S. Gupta, K. Mishra, M. McNamara. Breast Cancer in Transgender Patients Following Medical and Surgical Intervention 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 PS4-09-17.
Gilbert et al. (Tue,) studied this question.