"Our study suggests that tamoxifen's metabolism, and possibly its effectiveness, can be modified by the genetic makeup of the person taking the drug and by the use of another drug prescribed to reduce tamoxifen-related hot flashes," says the study's senior author David Flockhart, M.D., Ph.D., director of the Division of Clinical Pharmacology at the Indiana University School of Medicine. "Our conclusions indicate that more extensive research is appropriate."

Tamoxifen, a drug that modifies the effect of estrogen on cells, is widely and effectively used in many women as part of standard therapy for those with breast cancer and those at high risk of developing the disease. For about 80 percent of the women who take tamoxifen, hot flashes are a side effect of the therapy and 45 percent of those women rate them as severe.

Drugs commonly prescribed to remedy the problem are new antidepressants, paroxetine and fluoxetine, which are selective serotonin reuptake inhibitors (SSRIs). SSRIs have been shown to inhibit the enzyme that breaks down tamoxifen into chemical agents called metabolites, including 4-hydroxy-tamoxifen, which was believed to be tamoxifen's most active metabolite.

Twelve women with a history of breast cancer, but no current evidence of the disease, were enrolled in a yearlong clinical trial. The women had to have taken tamoxifen for four weeks prior to enrolling in the trial, and remained on the therapy until the trial's conclusion. Each woman also took paroxetine for four weeks.

Extensive laboratory analysis of the women's blood plasma showed a significant decrease in a metabolite of tamoxifen after treatment with paroxetine.
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Contact: Mary Hardin
mhardin@iupui.edu
317-274-7722
Indiana University
2-Dec-2003