BOSTON — In addition to undergoing gender-affirming surgeries, transgender men and masculine-centered gender non-conforming individuals routinely pursue testosterone therapy to enhance masculine features. Testosterone therapy is generally considered safe in the short- and mid-term. However, little is known about the long-term effects the hormone may have on breast tissue.
In a first-of-its kind study published in Modern Pathology, a team of researcher-clinicians at Beth Israel Deaconess Medical Center (BIDMC) conducted a retrospective analysis to evaluate whether testosterone therapy was associated with changes in breast tissues, and if so, how long it took for these changes to take place.
"Unlike mastectomies performed in the context of breast cancer, chest-contouring surgery does not remove the entire mammary gland, and breast cancer can still potentially occur in residual breast tissue," said lead author Jan Heng, PhD, a staff scientist at BIDMC and an Assistant Professor of Pathology at Harvard Medical School. "The long-term impact of testosterone therapy on these hormone-sensitive breast tissues is poorly understood."
Heng and colleagues reviewed samples of breast tissue taken from transgender patients who underwent chest-contouring surgery at BIDMC between 2013 and 2019. Among the 447 patients, 367 had received testosterone therapy prior to the surgery, and 79 had not. The researchers gathered demographic data and medical history — including duration of testosterone therapy — from patients' electronic medical records.
Focusing on seven histologic features associated with testosterone therapy, the researchers' analysis suggested that, overall, testosterone therapy does not result in clinically significant changes in breast tissue even when patients take it for more than 12 months. One of the seven histologic features — lobular atrophy, a change associated with a lower risk of breast cancer — was significantly linked to longer duration of testosterone therapy; four other types were less likely to occur in patients taking testosterone therapy than in patients who were not taking the hormone.
Heng and colleagues also found high-risk cellular changes as well as cancer in 2.5 percent of patients receiving testosterone therapy. Taken together, the researchers' findings shed new light on testosterone therapy's effect on breast tissues, and suggest that physicians should consider routine, culturally-sensitive, breast cancer screening for transgender men and non-gender conforming individuals.
"Identifying breast cancer risk factors unique to the transgender men and the non-gender conforming community as well as establishing screening protocols will be important," said Heng. "It remains unclear to what extent breast cancer risk is modified after testosterone therapy in combination with gender affirming surgeries. Ultimately, studying the molecular underpinnings of how testosterone therapy modulates breast biology and cancer risk could enable us to identify biomarkers of importance to the transgender population that may also be applicable for breast cancer prevention in cisgender women as well."
