Some Tamoxifen Side Effects Explained

Research has revealed why tamoxifen protects against breast cancer, yet increases risks for uterine cancer.

Tamoxifen is used to prevent the return of estrogen-dependent breast tumors. Tamoxifen blocks estrogen action in the breast, slowing or preventing breast cancer in many situations; however, research finds that tamoxifen increases uterine cancer risks, according to NewsFix.

Researchers at the Dana-Faber Cancer Institute found that secondary molecules are sent to a site on a cell when tamoxifen binds to the cell. The team compared this response in tamoxifen with that of raloxifene, a drug not associated with increased uterine cancer risks, NewsFix reported. Tamoxifen “recruits” the molecules that provoke cell division, which increases risks for cancer; raloxifene recruits repressor molecules, which do not create cell division, according to NewsFix

We previously wrote that more than 500,000 women in the United States are taking tamoxifen and about 30 percent of those women are also prescribed antidepressants to treat hot flashes.

Hot flashes are a common side effect of tamoxifen therapy and doctors started using antidepressants for hot flashes after hormone-based treatments were linked to the development of breast cancer. Treating tamoxifen hot flashes with antidepressants is an off-label use of such drugs.

A prior study conducted by Medco Health Solutions Inc. found that breast cancer patients who took an antidepressant like Paxil, Prozac, or Zoloft with tamoxifen were more than twice as likely to have their cancer return. The study, which involved 1,300 women, found that those who took such drug combinations for one year experienced a breast cancer recurrence rate of 16 percent compared to a recurrence rate of 7.5 percent for women not taking the drugs.

Not all antidepressants had the same impact. The study revealed that women on drugs like Celexa, Lexapro, and Luvox did not have a statistically higher rate of cancer recurrence.

Tamoxifen works by combining with the CYP2D6 enzyme, which is produced by the liver. This produces endoxifen, a substance known to fight tumors. But some antidepressants, including Paxil, Prozac, and Zoloft, block the CYP2D6 to varying degrees, which likely impacts the efficacy of tamoxifen.

Prior to the Medco study, laboratory studies revealed that some antidepressants could impact tamoxifen. The U.S. Food and Drug Administration had already taken a look at interactions between tamoxifen and antidepressants.