Conflicting Data on Breast Cancer, Tamoxifen and Antidepressants Emerge

ORLANDO, Fla., May 31, 2009— -- Thousands of breast cancer survivors take antidepressants to ward off hot flashes caused by tamoxifen, a chemical agent that helps prevent the disease from returning.

But some researchers worry about the mix: They think some popular antidepressants may keep the anti-cancer drug from working as well as it should.

Doctors and patients hoped two large studies would resolve the issue, but they were disappointed this weekend: Scientists in the United States and the Netherlands reached opposite conclusions at the annual meeting of the American Society for Clinical Oncology.

The antidepressants, known as selective serotonin reuptake inhibitors (SSRIs), are a class of drugs that includes fluoxetine (best known under the brand name Prozac) and paroxetine (Paxil).

One particular group of these antidepressants works by inhibiting an enzyme known as CYP2D6, which coincidentally helps the body process tamoxifen. Researchers want to know if the potential for conflict between the two agents yields real problems for breast cancer survivors.

In the U.S. study, an analysis of medical records of almost 1,000 breast cancer patients showed that use of CYP2D6 inhibitors almost doubled the risk of breast cancer recurrence within two years after patients started tamoxifen.

The records showed a two-year breast cancer recurrence rate of 13.9 percent in women taking tamoxifen along with a CYP2D6 inhibiting antidepressant, compared with a 7.5 percent recurrence rate among women taking tamoxifen alone, according to Dr. Ronald E. Albert of Medco Health Solutions in Franklin Lakes, N.J.

In contrast, Dutch investigators reported just the opposite when they looked at the records of 1,962 breast cancer patients who took tamoxifen between 1994 and 2006. They found no evidence that CYP2D6 inhibitors increased the risk of breast cancer recurrence in women taking tamoxifen.

In fact, during more than four years of follow-up, the group taking CYP2D6 antidepressants had a recurrence rate of 13.3 percent, compared to 14.6 percent among women who took tamoxifen alone or took a CYP2D6 inhibitor for less than 60 days while on tamoxifen.

Studies Conflict on Antidepressants' Effect on Breast Cancer Recurrence

"Based on our findings and previous studies, we don't have strong evidence that it's unsafe to use 2D6 inhibitors during tamoxifen therapy," Dr. Vincent Dezentje of Leiden University Medical Center, said in a statement.

None of this pleased physicians who were looking for a definitive answer. Noting that the number of women who took both tamoxifen and CYP2D6 antidepressants was relatively small in both studies, they called for research involving larger groups.

"We still have a lot of work to do," said Dr. Lori Pierce, a breast cancer specialist at the University of Michigan, who was not involved in either study. "These two conflicting studies show that we still don't have a definite answer about how important CYP2D6 function is. We need to do more validative studies to find out whether or not we should be testing women [for CYP2D6 status] who are on tamoxifen."

Until the issue is resolved, Pierce added, women taking tamoxifen have alternatives to CYP2D6 inhibitors. Some SSRIs do not inhibit the enzyme. Using a different drug known as an aromatase inhibitor instead of tamoxifen to prevent breast cancer recurrence is another possible option.

"You should make the best judgment in terms of the appropriate medication for the patient, given her disease," said Pierce. "There are ways to work around the problem if tamoxifen is the best drug for a patient. But certainly aromatase inhibitors are very important drugs in our armamentarium for postmenopausal women with breast cancer."

One or more investigators in the U.S. study disclosed financial relationships with LabCorp, Medco Health Solutions, Roche Molecular Diagnostics, and Roche Molecular Solutions. Investigators in the study included Medco employees. Investigators in the Dutch study reported no disclosures.