ORLANDO, Fla. - Breast-cancer survivors risk having their disease come back if they use certain antidepressants while also taking the cancer-prevention drug tamoxifen, worrisome new research shows.

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 are not 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 yesterday at an American Society of Clinical Oncology 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 that 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 Eric Winer, breast-cancer chief at the Dana-Farber Cancer Center in Boston.

He had no role in the study, which was conducted 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 Paxil and Prozac, and, to a lesser extent, Zoloft.

No greater risk of breast cancer was seen in women taking Celexa, Lexapro or Luvox with tamoxifen, and there are reasons to think other antidepressants may be safe as well, said Robert Epstein, Medco's chief medical officer.

A second study led by Vincent Dezentj of Leiden University Medical Center in the Netherlands found little risk from combining tamoxifen and popular antidepressants. But only 150 women in the study took such combos for more than two months, and they were compared with women taking combos for a shorter time - not with women using tamoxifen alone.

The Food and Drug Administration has been considering a change to tamoxifen's label to warn about the antidepressant drugs. An advisory panel unanimously recommended a change in 2006, but the FDA is still considering it.