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Genes, Antidepressants Can Affect Tamoxifen

Findings May Help Determine Which Women Respond Best to Breast Cancer Drug
WebMD Health News

Jan. 5, 2005 -- Scientists are one step closer to predicting which women will reap the greatest benefit from tamoxifen. The answer may lie in the women's genes -- and in their medicine chests.

Tamoxifen has been used for more than 20 years to treat breast cancer. It's also prescribed to help prevent breast cancer in women at high risk for the disease.

But tamoxifen isn't a magic bullet. Some patients have more success with it than others. To find out why, researchers studied 80 newly diagnosed women with breast cancer as they started taking tamoxifen.

The study was conducted by researchers including Yan Jin of Indiana University's medical school. It appears in the Jan. 5 issue of the Journal of the National Cancer Institute.

The scientists screened the patients' DNA. They focused on genes needed to break down tamoxifen. Those genes have dozens of variations. The researchers wanted to see which variations affected blood levels of tamoxifen.

The researchers also looked at whether the women were taking medications called selective serotonin reuptake inhibitors (SSRIs) and newer antidepressants, along with tamoxifen. SSRIs are antidepressants such as Paxil, Zoloft, and Prozac. SSRIs and other antidepressants such as Effexor are also prescribed to help handle hot flashes triggered by tamoxifen.

After the women had taken tamoxifen for four months, the results started coming in. The women with a genetic variation didn't break down tamoxifen as well as those without the variation. Their blood contained less of the active by-product called endoxifen, which comes from breaking down tamoxifen.

Women with the gene variations who also took SSRIs fared worse. They had 38% lower levels of the chemical in their blood than those not taking SSRIs. Thirty percent of the participants were taking SSRIs.

However, in some women with the normal gene who took tamoxifen along with an SSRI, levels of endoxifen were reduced by 58%.

The gene variations and SSRIs may work together to hamper tamoxifen. It's a chain reaction that starts with the genes, weakening their ability to break down tamoxifen.

Some antidepressants had stronger effects than others. For instance, Effexor had less of an impact on tamoxifen than Paxil.

More studies should help researchers learn which gene variations and drug combinations work best.

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