Some antidepressant medications may change the way the body processes tamoxifen, researchers report in this week's issue of the Journal of the National Cancer Institute (Vol. 97, No. 1:30-39). The effect may be especially great in women with a particular type of gene variation.

The researchers caution that it's too soon to know whether these interactions make tamoxifen less effective against breast cancer. And it's too soon to recommend genetic testing for the mutations identified in the study.

But women taking both tamoxifen and an antidepressant may want to talk with their doctor about switching to an antidepressant that has less of an effect on tamoxifen, said lead researcher David Flockhart, MD, PhD, of Indiana University School of Medicine.

"Women should not go off of tamoxifen or off antidepressants because of these findings," he said. "But with what we know now, we think [switching antidepressants] is a reasonable suggestion."

Flockhart and his colleagues studied 80 women who had just started taking tamoxifen after a diagnosis of breast cancer. Twenty-three of the women (29%) were also taking one of the following antidepressants: paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), fluoxetine (Prozac), or venlafaxine (Effexor). These drugs, known as selective serotonin reuptake inhibitors (SSRIs), are used to treat depression and can also help relieve the hot flashes that are a common side effect of tamoxifen therapy.

The researchers measured the level of tamoxifen and its byproducts in the women's blood after 4 months on the breast cancer drug.

The women using antidepressants were found to have lower blood levels of endoxifen, a tumor-fighting substance created when tamoxifen breaks down in the body. Paxil and Prozac lowered endoxifen levels the most, while Effexor lowered them least.

The researchers also compared endoxifen levels in women with different types of genetic variations. Women with specific variations in the CYP2D6 gene also had less endoxifen in their blood than other women. And the women with variations who also took antidepressants had even lower levels -- up to 58% lower.

Around 7% of whites and Hispanics, and around 3% of Asians and African-Americans, carry these gene variations, Flockhart said.

The researchers don't know if lower levels of endoxifen mean the tamoxifen isn't working as well as it might.

"We need more data related to outcomes -- [breast cancer] recurrence, disease-free survival, and so forth," Flockhart said.

For that reason, he and his colleagues do not yet recommend genetic testing for these variations.

For now, learning about the difference in genes is more of a step along the road to customized treatment, Flockhart explained. Doctors hope to use the information to develop tests that can help them predict which drug -- tamoxifen, an aromatase inhibitor, or Faslodex, for instance -- is likely to work best for a particular woman.

But switching to Effexor is a much easier precaution, Flockhart said, as long as a woman consults her doctor first.

"There are some women who derive important, almost life-saving, benefit from specific antidepressants," he said, "and we don't want women who have been successfully treated for a long period of time to compromise that treatment."