The Impact of Exogenous Testosterone on Breast Cancer Risk in Transmasculine Individuals

Background Exogenous testosterone is vital to gender-affirming therapy for transmasculine individuals. Testosterone may be implicated in breast cancer (BCa) because it can activate androgen and estrogen receptors. To further explore this risk, we performed a systematic review to investigate the impact of exogenous testosterone on BCa risk in transmasculine individuals. Methods We searched PubMed/MEDLINE and Ovid/Embase for clinical and preclinical studies assessing BCa and testosterone therapy and screened 6125 articles independently. We ascertained level of evidence using a modified tool from Cook et al (Chest. 1992;102:305S–311S) and risk of bias using a modified Joanna Briggs Institute's Critical Appraisal Tool. Results Seventy-six studies were included. Epidemiological data suggested that BCa incidence was higher in transmasculine individuals compared with cisgender men but lower compared with cisgender women. Histological studies of transmasculine breast tissue samples also demonstrated a low incidence of precancerous lesions. Interestingly, cases demonstrated that BCa occurred at a younger average age in transmasculine individuals and was predominantly hormone receptor positive. The mechanism for BCa in transmasculine individuals may be related to androgen receptor stimulation or conversion to estradiol. Serum studies reported varied estradiol levels associated with exogenous testosterone. Animal and in vitro studies demonstrated that testosterone was growth inhibitory but may induce proliferation at higher doses or with low estradiol levels. Conclusions Plastic surgeons play a critical role in providing gender-affirming care for transmasculine patients. The limited studies available suggest that this patient population has decreased risk for BCa when compared with cisgender women; however, any BCa that does occur may have different clinical presentations and underlying mechanisms compared with cisgender women and men. Overall, the limitations for clinical studies and discrepancies among preclinical studies warrant further investigation.