What do we know about breast cancer risk and testosterone therapy?

Evidence on the impact of testosterone on breast tissue and cancer risk is still emerging. Current studies have conflicting results on the impact of testosterone on breast cancer risk. Both androgens and estrogens can be drivers for breast cancer; it is important to note that excess testosterone aromatizes into estrogen-related compounds (Glaser & Dimitrakakis, 2015). Yet, exogenous testosterone may also result in ovarian insufficiency—suppressing the expression of endogenous estrogens—when used long-term (Spinder et al., 1989; Grimstad et al., 2020). Testosterone is known to be associated with histological changes that include lobular atrophy (Slagter et al., 2006; Tourous, Schnitt 2019).

What is important to know?

• Breast cancer still occurs in individuals on testosterone, including both those who have and have not had top surgery
• The exact effect of testosterone on breast cancer risk is presently unknown. Better studies are needed to quantify the impact on risk amidst confounding variables.
• Tissue changes may affect clinical exams due to palpable changes in tissue composition.
• Hormone therapy should not be withheld based on theoretical cancer risk, though informed discussion should be provided to patients at increased breast cancer risk.
• Hormone therapy should not be withheld in patients with breast cancer without consulting with a medical oncologist specializing in breast cancer (not a general oncologist) and an informed, patient-centered discussion.

Longitudinal cohort studies that measure and control for known confounding variables are needed to accurately determine the impact of testosterone on breast cancer risk.

Ultimately, the absolute risk with testosterone use is difficult to quantify without studies that examine:

• Whether the patient received puberty blockers
• Whether the patient experience estrogen vs. testosterone-dominant puberty (e.g., due to gender affirming care received in adolescence)
• Age of testosterone therapy initiation
• How body habitus impacts the histology and amount of breast tissue
• Testosterone dosage
• Individual factors such as total aromatase activity and androgen receptor expression
• Whether the patient has secondary ovarian insufficiency
• Whether the patient has had an oophorectomy
• Whether the patient has had gender-affirming top surgery
• Whether the patient has family history or genetic variants associated with breast cancer risk