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Some Antidepressants May Thwart Tamoxifen's Effect on Breast Cancer

Women should seek alternatives to SSRIs for hot flashes, studies suggest

SUNDAY, May 31 (HealthDay News) -- Common antidepressants that many breast cancer survivors use to dampen the hot flashes caused by taking tamoxifen may actually boost the odds of the disease's return, new research warns.

The finding was presented this weekend at the American Society of Clinical Oncology's annual meeting, in Orlando, Fla.

But to muddy the waters further, a second study found that the antidepressants did not impair tamoxifen's cancer-fighting powers.

Nevertheless, authors from both reports are recommending that women who have had breast cancer explore other ways to treat hot flashes.

Outside experts agreed.

"Women should talk to their medical oncologist about what antidepressant they're and what hormone therapy they're on, and make sure they're not one of the ones we're worried about," said Dr. Kelly Marcom, a breast oncologist with the Duke Comprehensive Cancer Center and director of the Duke Hereditary Cancer Clinic, in Durham, N.C.

Many breast cancer survivors take the drug tamoxifen to reduce their odds for recurrence. But tamoxifen often causes hot flashes, a side effect that can be controlled with selective serotonin reuptake inhibitor (SSRI) antidepressants such as paroxetine (Paxil) or fluoxetine (Prozac). Besides working on the neurotransmitter serotonin, these drugs inhibit an enzyme called 2D6, necessary to convert tamoxifen into its main active metabolite, endoxifen.

Women who have a gene mutation preventing the formation of 2D6 do not reap the same benefits from tamoxifen as women without the mutation, the researchers noted. Moreover, drugs that inhibit the formation of 2D6 may result in lower levels of endoxifen, although the clinical implications of that remain unclear.

The U.S. Food and Drug Administration is still weighing whether or not to add a caution about the gene variation to the tamoxifen label.

In one of the studies, Medco, a U.S. pharmacy benefits management company, reviewed the medical records of 10.7 million members of a health plan. That analysis turned up 945 women taking tamoxifen and 353 taking tamoxifen plus an SSRI/2D6 inhibitor, most commonly Prozac and Paxil.

Both groups of women, whose average age was in the early 50s, had followed similar treatment courses.

Women taking both drugs had a 13.9 percent chance of their breast cancer returning over two years, vs. just 7.5 percent of those receiving tamoxifen alone; that translates into an almost twofold increase in risk.

The second study, conducted by researchers at Leiden University Medical Center in the Netherlands, collected information on almost 2,000 breast cancer patients using tamoxifen, 215 of whom had used an SSRI/2D6 inhibitor at some point during their tamoxifen treatment.

That study found no increased risk of a breast recurrence in women taking both drugs. However, the authors pointed out, the number of women taking both drugs was small -- good enough reason for women and doctors to search for other options to combat hot flashes.

The Medco findings should serve as a warning but not a confirmation of any real danger to patients, one expert said.

"It's a study that is very difficult to interpret because it's really not complete enough information," said Dr. Claudine Isaacs, director of the clinical breast cancer program at Georgetown's Lombardi Comprehensive Cancer Center in Washington, D.C. "It raises a concern about this, and there's a scientific rationale to be concerned about. We can't say anything conclusively but there are options, other types of antidepressants, other types of medications, that don't have that impact. The cautious thing to do is to choose other medications while trying to sort this out."

Marcom agreed. He also noted that breast cancer-inhibiting medications called aromatase inhibitors, which include letrozole (Femara) and exemestane (Aromasin), "are one possible alternative to tamoxifen. There are also genotyping issues -- how different individuals metabolize the various drugs. This is not standard of care but it can be checked."

More information

There's more on tamoxifen at the U.S. National Cancer Institute.

SOURCES: Claudine Isaacs, director, clinical breast cancer program, Georgetown's Lombardi Comprehensive Cancer Center, Washington, D.C.; P. Kelly Marcom, M.D., breast oncologist, Duke Comprehensive Cancer Center, and director, Duke Hereditary Cancer Clinic, Durham, N.C.; May 30, 2009, presentations, American Society of Clinical Oncology annual meeting, Orlando, Fla.

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