Androgen Receptor Agonism in Estrogen Receptor–Positive Breast Cancer
Posted: Wednesday, April 8, 2020
The androgen receptor appears to act as a tumor suppressor in estrogen receptor–positive breast cancer, according to a recent preclinical study, and thus may prove to be an effective therapeutic option for this type of cancer. The study, which was originally slated to be presented at the 2020 Endocrine Society Annual Conference (ENDO 2020; Abstract OR05-06), was conducted by Wayne Tilley, PhD, of the University of Adelaide, Australia, and colleagues.
“There is a prevailing assumption that the androgen receptor promotes malignancy in breast cancer, as it does in prostate cancer,” Dr. Tilley commented in an Endocrine Society press release. “Our study demonstrates that this is not the case for estrogen receptor–driven breast cancer.”
The researchers hypothesized that, because breast tissue growth is inhibited by androgen and promoted by estrogen, the androgen receptor likely suppresses tumor development in estrogen receptor–positive breast cancer. A multitude of cell line, patient-derived explant, and xenograft breast cancer models were tested to examine the effects of androgen receptor agonism. Samples from patients with tumors resistant to current therapies, and samples with abnormalities of ESR1 were also analyzed.
The results of the study provided evidence that androgen receptor agonism inhibited tumor growth through the downregulation of genes involved in the cell cycle. The agonist-bound androgen receptor repositions the estrogen receptor and the co-activator p300, which may lead to the opposition of estrogen receptor signaling. When tested in combination with estrogen receptor–targeted therapies such as tamoxifen or a CDK4/6 inhibitor, tumor growth was further inhibited. This inhibition occurred even in tumor cells that were resistant to current therapies. Additionally, the researchers created an androgen receptor signature that outperformed existing prognostic signatures.
“Treatment of estrogen receptor–positive breast cancer with an androgen receptor activator drug could be immediately tested in women,” Dr. Tilley proposed.
Disclosure: The study authors’ disclosure information can be found at endocrine.org.
