About 500,000 women in the United States take tamoxifen, which cuts in half the chances of a breast cancer recurrence. Many of them also take antidepressants for hot flashes, because hormone pills aren't considered safe after breast cancer.
Doctors have long known that some antidepressants and other medicines can lower the amount of tamoxifen's active form in the bloodstream. But whether this affects cancer risk is unknown.
The new study, reported Saturday at a cancer conference in Florida, is the largest to look at the issue. It found that using these interfering drugs - including Prozac, Paxil or Zoloft - can virtually wipe out the benefit tamoxifen provides.
Many doctors question the magnitude of harm from combining these medicines, and a second, smaller study suggests it may not be very large.
But the bottom line is the same: Not all antidepressants pose this problem, and women should talk to their doctors about which ones are best.
"There are other alternatives we can consider" that are safer, said Dr. Eric Winer, breast cancer chief at the Dana-Farber Cancer Center in Boston.
He had no role in the study, which was done by Medco Health Solutions Inc., a large insurance benefits manager. Researchers used members' medical records to identify 353 women taking tamoxifen plus other drugs that might interfere with it, and 945 women taking tamoxifen alone. Those taking a drug combo did so for about a year on average.
Next, researchers checked to see how many were treated for second cancers in the following two years. Breast cancer recurred in about 7 percent of women on tamoxifen alone, and in 14 percent of women also taking other drugs that could interfere - mainly the antidepressants Paxil and Prozac, and, to a lesser extent, Zoloft.
If women want to take an antidepressant, "you probably want to stay away from those three," said Medco's chief medical officer, Dr. Robert Epstein.
No greater breast cancer risk was seen in women taking the antidepressants Celexa, Lexapro or Luvox with tamoxifen, and there are reasons to think that other antidepressants may be safe as well, Epstein said.
A second study led by Dr. Vincent Dezentje of Leiden University Medical Center in the Netherlands found little risk from combining tamoxifen and popular antidepressants. However, only 150 women in the study took such combos for more than two months, and they were compared to women taking combos for a shorter time - not to women using tamoxifen alone.
The Dutch and Medco studies were presented at a meeting of the American Society of Clinical Oncology.
The federal Food and Drug Administration has been considering a change to tamoxifen's label to warn about the antidepressants drugs and a gene variation some women have that can make tamoxifen less effective. An advisory panel unanimously recommended a change in 2006, but the agency is still considering it.
"This is a very controversial area," said Dr. Claudine Isaacs, a breast specialist at Georgetown University's Lombardi Comprehensive Cancer Center. "Until these data are absolutely clear, I would avoid drugs that impact on tamoxifen metabolism."
Breast cancer is the most common major cancer in American women. More than 182,000 new cases were diagnosed last year, and it caused nearly 41,000 deaths.