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Research Reveals Why Tamoxifen Doesn't Always Work

Receptors on the surface of breast cancer cells may be the key, scientists say

THURSDAY, Oct. 30 (HealthDay News) -- Scientists have uncovered new clues to how breast cancer cells become resistant to the widely-used prevention and treatment drug tamoxifen.

The findings, from a team at Georgetown University Medical Center (GUMC), in Washington, D.C., could provide a way to identify tamoxifen users who have become resistant, so that doctors can try a better treatment option sooner.

According to the study, tamoxifen-resistant breast cancer cells display few of the "alpha" estrogen receptors that the drug is designed to bind with and inhibit. Instead, they display many more "gamma" estrogen-related receptors, which tamoxifen appears to activate, the researchers said.

The Georgetown group also tracked how, as tamoxifen resistance increases, breast cancer cells gradually lose their alpha receptors while gaining more estrogen-related gamma receptors.

The study, published in the Nov. 1 issue of the journal Cancer Research, offers two important new insights, according to lead author Rebecca Riggins, research assistant professor of oncology at GUMC's Lombardi Comprehensive Cancer Center.

First, it gives 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. All that was known is that there were more of these receptors in breast cancer than in normal breast tissue, we hadn't got much further than that," Riggins said in a GUMC news release.

The findings could also help explain why invasive lobular carcinoma -- the subtype of breast cancer examined in this study -- may not respond as well to tamoxifen as other breast cancer subtypes.

"It is unclear whether tamoxifen is very effective in this cancer, and has been a point of debate among clinicians. This study is a good first step toward clarifying the role that tamoxifen resistance apparently plays in treatment of invasive lobular cancer," Riggins said.

More information has more about tamoxifen.

-- Robert Preidt

SOURCE: Georgetown University Medical Center, news release, Oct. 30, 2008

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