Systematic Review on Gender-Affirming Testosterone Therapy and the Risk of Breast Cancer: A Challenge for Physicians Treating Patients from Transgender and Gender-Diverse Populations

Conflicting evidence exists about the risk of breast cancer in transgender and gender-diverse (TGD) patients treated with testosterone. This review aimed to summarize current knowledge regarding the risk of breast cancer associated with gender-affirming testosterone treatment (GATT). A systematic literature search using the Preferred Reporting Items for Systematic Review and Meta-Analysis checklist was conducted in January 2023 through Ovid, Scopus, and Web of Science databases. English-language, peer-reviewed articles evaluating breast cancer in TGD patients after GATT that met the inclusion criteria were included. This review included 22 articles, with 14 case reports, 4 case series, and 4 retrospective cohort studies. The review identified 26 TGD patients who developed breast cancer post-GATT therapy, with inconclusive evidence on the relationship between testosterone and the risk of breast cancer in TGD patients. This uncertainty in part arises from the mechanisms governing testosterone's effects within breast tissue, with contrasting theories proposing both proliferative and antiproliferative impacts. Considering this ambiguity, it is imperative for healthcare providers to engage in informed discussions with patients prior to initiating hormone therapy to discuss potential adverse effects, including the possibility of breast cancer development in TGD individuals. Patient education and shared decision-making are essential components of responsible care in this context.