Possible new weapon found for fighting some types of breast cancer

Researchers believe they have discovered one reason why some women with estrogen receptor-positive breast cancer may respond poorly or only temporarily to estrogen-blocking drugs such as tamoxifen. Results of a new study, which was presented Saturday at the joint meeting of the International Society of Endocrinology and the Endocrine Society: ICE/ENDO 2014 in Chicago, point to a previously unrecognized role of the androgen receptor.

Although this receptor (protein) is expressed in nearly all prostate cancers, it also is expressed in most breast cancers. Now scientists have found that estrogen receptor alpha—a main driver of estrogen-fueled —may rely on the androgen receptor for its function.

In a study funded by the U.S. Department of Defense Breast Cancer Research Program, Jennifer Richer, PhD, from the University of Colorado Anschutz Medical Campus in Aurora, and her colleagues studied 192 women with estrogen receptor-positive breast cancers. They found that women were 4.4 times more likely to have a cancer recurrence during tamoxifen treatment when their main tumor had a high ratio (2:1 or greater) of androgen receptor-positive cells to estrogen receptor-positive cells.

"Women with breast cancer do not routinely receive testing for the androgen receptor," Richer commented.

The investigators hypothesized that maximal estrogen receptor activity depends on the androgen receptor's nuclear localization. This process, Richer said, involves the receptor moving itself and the hormone molecule, to which it is bound, inside the nucleus of a cell, where the receptor "does its important business."

Richer and her co-workers then tested a new anti-androgen drug called enzalutamide, which is approved for treatment of prostate cancer. Unlike older anti-androgen drugs, which allow the androgen receptor to go to the cell's nucleus, enzalutamide inhibits the ability of to enter the nucleus, Richer said.

"If the androgen receptor is outside the nucleus, both estrogen and androgen driven tumor growth is inhibited," she explained.

In preclinical models (human cells and mice) of estrogen receptor-positive breast cancers that also were positive for the androgen receptor, enzalutamide treatment inhibited both androgen- and estrogen-controlled tumor growth, Richer reported. Further, the combination of enzalutamide and tamoxifen decreased estrogen-driven tumor growth better than either drug alone.

Another study by Richer's team, to be presented Monday (OR38-2), found that breast cancers that are estrogen receptor negative ("triple negative") can also rely on the androgen receptor for growth. In preclinical models of -negative tumors, enzalutamide treatment decreased by 85 percent, according to the abstract.

"Our research suggests that the androgen receptor may serve as a therapeutic target in both receptor-positive and negative breast cancers," Richer said.

Related Stories

New target, new drug in breast cancer

date Jun 04, 2012

Many breast cancers depend on hormones including estrogen or progesterone for their survival and proliferation. Eight years of lab work at the University of Colorado Cancer Center and elsewhere suggest that the androgen (AR) ...

Clinical trial hits new target in war on breast cancer

date Dec 03, 2012

Breast cancers are defined by their drivers – estrogen and progesterone receptors (ER and PR) and HER2 are the most common, and there are drugs targeting each. When breast cancer has an unknown driver, it also has fewer ...

Recommended for you

What's the harm in alternative therapies?

date 2 hours ago

We often see stories in the media about cancer patients who have chosen alternative treatments, either alongside or instead of conventional treatment.

'Chemo brain' is real, say researchers

date 23 hours ago

UBC research shows that chemotherapy can lead to excessive mind wandering and an inability to concentrate. Dubbed 'chemo-brain,' the negative cognitive effects of the cancer treatment have long been suspected, ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.