Testosterone treatments could reduce risk of breast cancer

Research into the effects of testosterone on breast tissue in transgender men may have implications for understanding and treating breast cancer.

Researchers at Cedars Sinai Medical Centre in Los Angeles, California, used tissue from transgender men who underwent mastectomy surgery to better understand the molecular changes that androgens can have on breast tissue. They observed that cells exposed to testosterone showed fewer signs of being influenced by oestrogen, a hormone that can drive some types of breast cancer.

'These findings build upon previous work showing androgen receptor activation suppresses tumour growth in oestrogen receptor-positive breast cancer,' said Dr Simon Knott, senior author of the study which was published in Cell Genomics. 'Androgens seem to counteract the effects of oestrogen and could potentially be used to prevent oestrogen-driven breast cancers.'

Androgens are hormones such as testosterone, they are naturally present in people of both sexes but are particularly associated with male sexual development. Some people who were assigned female at birth but identify as male or non-binary receive androgen therapy as part of their transition, to induce the development of masculine characteristics. Some of these people also have breast tissue removed as part of gender-affirming surgery.

To study the molecular effects of androgen therapy, researchers compared breast tissue samples from nine transgender men who had androgen therapy prior to surgery, with samples obtained from cosmetic breast surgeries in women who had not taken androgens.

They used single-cell nuclear RNA sequencing to look at gene expression, chromatin analysis to examine epigenetic changes, and spatial tissue profiling to reveal how androgen therapy reorganises cells within the breast tissue.

'We have created an atlas of every type of breast cell undergoing androgen therapy,' said first author Florian Raths. 'This database can be used by other investigators to study cellular changes following androgen exposure.'

The androgen-exposed tissues displayed increased activity of androgen receptor genes, and despite only a small proportion of cells displaying an androgen receptor they observed a related increase in communication between cells sensitive to androgen and neighbouring cells.

The results suggest that breast cells from transgender men have gene expression patterns similar to those seen in cisgender men. Changes include reduced expression of genes associated with milk production and upregulation of CUX2, a gene typically expressed in the prostate.

Additionally, the breast tissue of transgender men exhibited increased amounts of CD4 T-cells – a type of white blood cell – implying enhanced immune surveillance to defend against cancer.

Clinical trials are already investigating the use of androgens in breast cancer treatment, but the researchers suggest that in future it could also be used preventatively for individuals at high risk of developing breast cancer.