'New' estrogen receptor found to be key player in tamoxifen ...( Washington D.C. Researchers at Geo...)

Washington, D.C. Researchers at Georgetown University Medical Center have discovered a novel way in which breast cancer cells become resistant to tamoxifen, the world's largest-selling breast cancer prevention and treatment drug. They say the findings could provide a way to identify tamoxifen users who are no longer benefiting from the drug, allowing doctors to try another therapy option sooner.

In the November 1 issue of the journal Cancer Research, the researchers show that breast cancer cells that are resistant to tamoxifen display few of the "alpha" estrogen receptors that the drug is designed to bind on to and inhibit, but many more "gamma" estrogen-related receptors, which tamoxifen seems to activate. These two receptors are not closely related they are more like distant cousins than siblings, researchers say, adding that understanding how these gamma estrogen-related receptors work may eventually help in designing new, more effective drugs targeting these receptors.

In fact, they track how, as resistance develops over time, breast cancer cells gradually lose the alpha receptors while gaining the estrogen-related receptor gamma subtype.

The study offers two new insights, according to lead author Rebecca Riggins, Ph.D., a research assistant professor of oncology at GUMC's Lombardi Comprehensive Cancer Center.

One is a clearer understanding of the importance of the gamma estrogen-related receptor in breast cancer. "Until now, this receptor has not been viewed to be of much importance in any type of breast cancer," Riggins says. "All that was known is that there were more of these receptors in breast cancer than in normal breast tissue, we hadn't gone much further than that."

A second important insight is that the discovery could help explain why invasive lobular carcinoma the sub-type of breast cancer in which these findings were made may not respond as well to tamoxifen as perhaps other subtypes do, she says.

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