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Gene May Undermine Tamoxifen's Effectiveness

Ten percent of white breast cancer survivors carry the mutation, researchers say

MONDAY, Dec. 19, 2005 (HealthDay News) -- A common gene mutation may render the cancer-preventing drug tamoxifen less effective in preventing tumor recurrence in some breast cancer survivors, a new study suggests.

This genetic change in the CYP2D6 gene lowers levels of an important liver enzyme called Cytochrome P4502D6, which is responsible for tamoxifen metabolism, according to researchers at the Mayo Clinic and the University of Michigan.

Up to 10 percent of white patients may have this genetic change and these women are nearly twice as likely as other women to suffer a cancer relapse while receiving tamoxifen, the study found.

The findings appear in the Dec. 20 issue of the Journal of Clinical Oncology.

"Cytochrome P4502D6 has recently been shown to be a crucial enzymatic step responsible for activating tamoxifen to a metabolite that is nearly one hundred times more potent than tamoxifen," study co-author and Mayo Clinic oncologist Dr. Matthew Goetz said in a prepared statement.

"Our study demonstrates that women who inherit a genetic change in the CYP2D6 gene that lowers the level of this enzyme appear to be at higher risk of relapse when treated with five years of tamoxifen," he said.

"In addition to being at higher risk of relapse, the women with the genetic change also did not develop one of the most common side effects of tamoxifen -- hot flashes. These findings are important, as doctors commonly prescribe drugs such as antidepressants for the treatment of hot flashes, and many of these drugs potently inhibit the metabolism of tamoxifen," Goetz said.

More information

The U.S. National Cancer Institute has more about tamoxifen.

SOURCE: Mayo Clinic, news release, Dec. 16, 2005
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