Evidence increasing that breast cancer is driven by androgen

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Receptors for estrogen and progesterone and the gene HER2 are the big three markers and targets in breast cancer. New evidence is adding a fourth: androgen receptors (AR).

The finding of androgen receptors as a potential target in breast cancer is especially important in light of its prevalence in breast cancers that do not express other hormone receptor targets or have developed resistance to treatments that target estrogen dependence. Overall, approximately 77% of breast cancers are positive for AR, including 88% of estrogen-receptor positive (ER+) cancers, 59% of HER2 positive cancers, and 20% of 32% of triple-negative breast cancers.

"This is a continuing line of work with all evidence pointing toward the addition of the androgen receptor as potential target and useful marker in all of the major subtypes of breast cancer," said Jennifer Richer, PhD, investigator at the University of Colorado Cancer Center and codirector of the CU Cancer Center Tissue Processing and Procurement Core in Denver.

The study was presented at the American Association for Cancer Research (AACR) Annual Meeting 2013 in Washington, DC. It explored the ability of ER+ breast cancers to develop resistance to anti-estrogen drugs by potentially developing an alternative addiction to AR, and it hypothesized that antiandrogen therapy, such as the drug enzalutamide (formerly MDV3100), could be successful counters to breast cancers' evolution.

First, Richer and colleagues used breast cancer tumor registries to discover that cancers with higher ratios of AR to ER protein had shorter time to relapse after antiestrogen therapies. Cut off from their estrogen addition, these cancers may have turned to growth and survival via androgens instead. The group then returned to the lab to explore the effects of antiandrogen therapies in cell lines and preclinical models.

"Remarkably, the antiandrogen drug enzalutamide had effects comparable to the antiestrogen drug tamoxifen in breast cancer cells that expressed both ER and AR," Richer said. HER2 cell lines that were also AR+ showed promising responses as well.

"We are excited to move toward clinical trials of antiandrogen therapies in breast cancer," Richer said. "And this study shows that patients with a high AR/ER ratio who relapse while on estrogen targeting therapies might be good candidates for this kind of therapy."

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