Purpose: The majority of transmasculine individuals pursue testosterone therapy (TT) to affirm their gender identity. Long-term exposure to high-dose exogenous testosterone raises concerns about its potential carcinogenic effect on breast tissue. Testosterone therapy modulates breast histology, however, it is unknown whether TT alters breast tissue density, and in turn, the breast cancer risk of transmasculine individuals. In this pilot study, we investigate the relationship between the duration of TT and breast tissue density in transmasculine individuals, with both qualitative and quantitative metrics.
Materials and Methods: We established an IRB approved retrospective transmasculine research cohort of 444 patients who underwent chest-contouring surgeries from 2013-2019. Clinical data including duration of TT, breast cancer risk factors commonly studied in cisgender women, and breast imaging data were collected. As most patients were young (median age of 25; range=18-61), only 42/444 (9.5%) had mammograms taken between 0.4-34.9 months prior to surgery. Breast tissue density assessments were available for all 42 patients and DICOM mammogram images (2-3 mediolateral oblique views) were available for 25/42 (59.5%). These DICOM images were processed with LIBRA software and average %breast density was calculated.
Results: Among the 42 individuals (median age of 43; range=20-61) with pre-operative mammograms, 6 (14.3%) had fatty breasts, 13 (31.0%) had scattered fibroglandular densities, 18 (42.9%) had heterogeneously dense breasts, and 5 (11.9%) had extremely dense breasts (Table 1). There was no association between TT (yes/no) and breast tissue density among all individuals (p=0.63), or within individuals <40 years old (p=0.91) or ≥40 years old (p=0.88; Fisher’s Test). There was also no association between duration of TT (median=8.0 months; range=0-59.7) and breast tissue density (p=0.93, Kruskal-Wallis test; Figure 1). Radiologist reported breast tissue density was significantly correlated with calculated average %breast density (rho = 0.67; p<0.001; Figure 2). There was no association between TT (yes/no) and %breast density (β=-1.52, p=0.20) or when the linear regression model accounted for age at mammogram and BMI at surgery (β=-0.39, p=0.69). Similar null associations were also observed between duration of TT and %breast density (crude β=-0.04, p=0.14; adjusted β=-0.01, p=0.52).
Conclusion: In this pilot study, gender-affirming testosterone therapy does not appear to affect the breast tissue density of transmasculine individuals. Larger studies are needed to confirm these findings.
Clinical Relevance Statement: Characterizing breast tissue density in transmasculine people will clarify the effect of testosterone therapy on breast tissue density, improve understanding of their breast cancer risk factors, and support the development of screening guidelines for this vulnerable community.
