Abstract PR009: Effect of testosterone therapy on quantitative breast lobular atrophy in transmasculine individuals
Authors: Baker Gabrielle M. , Guzman-Arocho Yaileen D. , Bret-Mounet Vanessa C. , Veta Mitko , Wetstein Suzanne C. , Charlton Brittany M. , Jackson Sarah S. , Wulf Gerburg M. , Heng Yujing Jan 
Published: December 2023

Abstract
Background. Most transmasculine (TM) individuals pursue gender-affirming testosterone therapy (TT). The health outcomes associated with long-term TT use remains unclear. We previously reported that TT is associated with breast lobular atrophy (i.e., shrinking) when assessed by pathologists. Breast lobules are the main sites whereby cancer develops, and there are ongoing research to clarify the association between lobular atrophy and breast cancer risk. As such, TT may influence breast cancer risk in TM individuals. This study investigated the quantitative relationship between length of TT use and lobular atrophy. Materials and Methods. Breast surgical specimens were obtained from 417 TM subjects who had gender affirming chest-contouring surgery. Clinical data were retrieved from medical records. Each subject had one to six H&E slides that were reviewed by pathologists and digitized at 20× (n=1073 whole slide images (WSIs)). We applied our deep-learning computational pathology method that detects and quantifies acini and breast lobules to the WSIs. For each WSI, our method extracted total tissue area (mm2), fat area (mm2), number of breast lobules, area (mm2) and span (mm) of each lobule, and the number of acini in each lobule. Multiple WSIs for each subject were combined to compute four measures of lobular atrophy—1) median lobule size (mm2), 2) median acini counts per lobule, 3) number of lobules per mm2 of tissue area, and 4) % lobular area. We evaluated the relationship between quantitative measures of lobular atrophy for every six months of TT use with linear regression models, adjusting for age, year of surgery, race/ethnicity, BMI, chest binding, whether the subject removed their ovaries, and TT dose. Patients who did not use TT prior to surgery were assigned as zero months of TT. In order to improve the interpretability of the beta coefficient, we back transformed the natural log beta coefficients. Results. The size of breast lobules in TM individuals shrank by 3.9 % for every six months of TT use (adjusted p&lt;0.001). The results of the other three measures were similar: the median number of acini in each breast lobule decreased by 5.5%, the number of lobules per mm2 of breast tissue decreased by 4.9%, and the % of lobular area in the breast was reduced by 10.0%, for every six months that a patient received TT (all adjusted p≤0.001). Conclusions. This is the first study to investigate the quantitative relationship between duration of TT and lobular atrophy. For every six months of TT, the breast lobules of TM subjects decreased in size and numbers at an approximate rate of 5%, after accounting for potential confounders. This work will support the understanding of breast cancer risk in the TM population, and contributes to reducing healthcare disparities in the transgender community.
Citation Format: Gabrielle M. Baker, Yaileen D. Guzman-Arocho, Vanessa C. Bret-Mounet, Mitko Veta, Suzanne C. Wetstein, Brittany M. Charlton, Sarah S. Jackson, Gerburg M. Wulf, Yujing Jan Heng. Effect of testosterone therapy on quantitative breast lobular atrophy in transmasculine individuals [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr PR009.