Gender-affirming testosterone therapy may have a potential protective benefit in transmasculine patients at risk of breast cancer, according to a recent study published by Heng et al in Breast Cancer Research.
Background
To treat their gender dysphoria, some transmasculine patients undergo chest-contouring surgeries, the primary goal of which is to create a male-appearing chest, not to remove all grossly identifiable breast tissue. While chest-contouring surgery can reduce the risk of breast cancer, the risk cannot be eliminated because residual breast tissue remains hormonally responsive.
Prior research using an artificial intelligence (AI) algorithm demonstrated that patients with higher amounts of breast epithelium may have an increased risk of breast cancer.
Most breast cancers arise in the breast epithelium—which is known to be highly sensitive to sex hormones. Increases in estrogen can stimulate epithelial cell proliferation, whereas testosterone may have antiproliferative effects that reduce the risk of cancer. As part of gender-affirming testosterone therapy, baseline testosterone levels of transmasculine patients are supplemented to match the levels observed in cisgender men and gain secondary sex characteristics. However, excess testosterone can be converted to estrogen in the body. As a result, it is currently unknown whether testosterone therapy may increase the risk of breast cancer by contributing to more estrogen in the body.
Study Methods and Results
In the recent study, the researchers examined the effects of gender-affirming testosterone therapy in the breast tissue of 425 transmasculine patients. They leveraged an AI algorithm to analyze the patients’ breast tissue composition—the relative amounts of breast epithelium, fibrous stroma, and fat.
The researchers found that the amount of breast epithelium in transmasculine patients who used testosterone therapy was 28% lower compared with those who didn’t use testosterone therapy. Further, testosterone therapy didn’t affect the amount of fibrous stroma and fat. Additional analyses revealed that the effect of testosterone therapy on reducing the amount of breast epithelium was less pronounced in patients with overweight or obesity.
Conclusions
The findings indicated that gender-affirming testosterone therapy could decrease the risk of breast cancer in this patient population.
The researchers suggested that the protective effect of testosterone may be offset by the endocrine activity of adipose tissue, such that testosterone therapy affects the breast cancer risk differently in transmasculine patients with overweight or obesity compared with those who have a normal weight.
Further studies may be needed to understand the complex relationship between testosterone, obesity, and breast cancer risk in transmasculine patients.
Disclosure: For full disclosures of the study authors, visit breast-cancer-research.biomedcentral.com.
