New Study on Androgens May Lead to Breast Cancer Treatments

Breast cancer cells

Breast cancer cells stained for the estrogen receptor (green) and the androgen receptor (red) that mediate the critical cancer promoting actions of estrogen and the protective effects of androgens in the breast, respectively.

An international collaborative study involving University of Adelaide and Cedars-Sinai Medical Center researchers has revealed new insights about hormonal treatment that could lead to the development of better breast cancer treatments.

The study, led by Cedars-Sinai investigators in the United States, concentrated on the effects androgen hormone therapy had on normal female breast tissue. It found the hormone changed the composition of immune cells, which could indicate the immune system is stopping the production of cancer cells.

Associate Professor Theresa Hickey from the University of Adelaide co-authored the study.

"While blocking androgen action is widely used in the treatment of prostate cancer, stimulating androgen action may be the best strategy for breast cancer. Based on our pioneering research published last year, there has been considerable worldwide interest in treating breast cancer with androgenic drugs, highlighting the need to better understand how this critical hormone works in both men and women."

"Our findings show that androgen hormone activity counteracts the effects of estrogen activity in the breast and could potentially be used to treat or prevent estrogen-driven breast cancer," she said.

The research published today in the peer-reviewed journal Cell Genomics focused on transgender men who were recorded as female at birth but identify as male and were undergoing gender-affirming androgen therapy.

"Breast tissue samples taken from transgender men were analysed and compared with samples from women who had undergone cosmetic breast surgery," said Associate Professor Hickey.

"We found breast cells in transgender males that normally react to estrogen showed fewer signs of being influenced by the hormone than the same cells taken from women who did not have the androgen therapy."

Androgens such as testosterone are primarily involved in the development of male traits, but women also produce them, and they are vital to female health.

The molecular and physical changes in the breast tissue of transgender men undergoing androgen therapy may indicate the potential for using androgen-like drugs to prevent or fight the most common type of breast cancer that is fuelled by estrogen.

Simon R. V. Knott, Assistant Professor of Biomedical Sciences and Medicine at Cedars-Sinai was senior author of the study.

"Changes stimulated by androgen are associated with activation of the androgen receptor, which binds to the hormone and relays signals to the cell that the hormone is present, and that it should change accordingly," he said.

"We found breast cells in transgender males that normally react to estrogen showed fewer signs of being influenced by the hormone than the same cells taken from women who did not have the androgen therapy."Associate Professor Theresa Hickey

The findings build on previous work by Professor Wayne Tilley's team at the University of Adelaide's Dame Roma Mitchell Cancer Research Laboratories, which has shown that androgen receptor activation suppresses tumour growth in estrogen receptor-positive breast cancer.

"The findings are exciting because they support our new approach using androgens (or androgen-like drugs) to activate the androgen receptor to more effectively treat or prevent breast cancer. Indeed, the findings indicate that our strategy will succeed because we are harnessing a natural pathway in the breast to oppose the tumour promoting action of estrogen," said Professor Tilley.

The breast samples were analysed using multiple new technologies to understand the type of cells and genes in the breast tissue that were affected by androgen. This allowed the investigators to understand which cells and genes were altered by the hormone.

The two research groups will continue to collaborate on how low doses of androgen given to women at high risk for estrogen-driven breast cancer affects their breast tissue at the molecular level. And they will examine how this could reduce breast cancer risk, especially in premenopausal women who have extremely limited options.

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