Study pinpoints mechanism behind tamoxifen side effect

BOSTON Researchers at Dana-Farber Cancer Institute have identified the underlying mechanism that causes one of the unwanted side effects of tamoxifen. The study, published in the March 29 issue of Science, may help researchers home in on new medications that, like tamoxifen, reduce the risk of certain types of breast cancer, but do not carry tamoxifens potentially dangerous downside.

Tamoxifen was the first drug shown capable of reducing the chances of breast cancer development in some women at risk for the disease, says Myles Brown, MD, Dana-Farber researcher and the studys senior author. But many women have been reluctant to take it because of potential side effects. By understanding the basic mechanism by which the drug works, we can look for medications whose profile of effects is more advantageous to patients.

Tamoxifen is currently used to lower the risk of breast cancer recurrence in women whose breast cell growth is fueled by the hormone estrogen. In the breast, tamoxifen acts as an anti-estrogen, blocking the hormone from latching onto cells and delivering a growth signal. In some other parts of the body, however, tamoxifen and estrogen have similar effects: both substances help strengthen womens bones, for example, and may help keep their cardiovascular systems healthy.

Unfortunately, estrogen and tamoxifen also have a common detrimental effect a heightened risk of the development of endometrial cancer. A nationwide study is under way to determine whether a drug called raloxifene, which may reduce breast cancer risk without raising the risk of endometrial cancer, prevents breast cancer as effectively as tamoxifen does.

Both tamoxifen and raloxifene belong to a class of substances known as selective estrogen receptor modulators, or SERMs, which bind inside cells at the same receptors that estrogen does. In some types of cells, such as those in bones and the cardiovascular system, the effects of this binding are similar for

Contact: Bill Schaller
Dana-Farber Cancer Institute

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