Originally created 07/10/98

Not enough evidence about tamoxifen



LONDON -- Contradicting U.S. findings, British scientists who conducted the longest-running study of tamoxifen have concluded there is not enough evidence the drug prevents breast cancer, according to research published Friday.

Although scientists agree tamoxifen fights the recurrence of breast cancer in women who already have had surgery, they are divided over whether it prevents the disease from occurring in the first place.

Part of the caution over use of the drug relates to its side effects, which include doubling the risk of getting uterine cancer and tripling the risk of developing a blood clot in the lungs, a potentially fatal disorder.

A U.S. National Cancer Institute study released in April said tamoxifen reduced the chances of breast cancer in high-risk women by 45 percent. It abandoned its trial of 13,388 women early to give every woman involved the option of taking the drug.

But researchers from the Royal Marsden Hospital in London, in a smaller but longer-running study, found the incidence of breast cancer among 2,494 women with a family history of the disease was the same regardless of whether they took the drug.

A separate study following 5,408 women for four years, conducted by the European Institute of Oncology in Milan, Italy, came to a similar conclusion. Both studies were published in The Lancet, a British medical journal.

"There are significant numbers of women requesting to take tamoxifen since the American study and I have grave concerns about the widespread use of it in healthy women," said Dr. Trevor Powles, leader of the British study.

Tamoxifen is known as an "anti-estrogen" because it blocks the effects of the hormone in some tissues and retards growth of cancer cells that depend upon estrogen.

Powles said the U.S. study results, which followed women for an average of three years, could mean tamoxifen was merely treating existing undetectable tumors rather than preventing new ones and it is unclear how effective the drug would have been if the study had continued for several more years.

In addition, he said, women who later develop tumors could be worse off if their cancer was resistant to tamoxifen, the most widely used drug for the treatment of the disease.

At the time the U.S. study was abandoned, the British scientists accused the National Cancer Institute of acting prematurely, and perhaps raising false hopes.

Powles said his study, which followed women for an average of eight years, does not conclude that tamoxifen does not prevent breast cancer, only that there is insufficient evidence to say it does.

After six years in the trial, 34 of the women on tamoxifen developed breast cancer, compared with 36 women on a placebo, the study said.

"We still believe tamoxifen will prevent a large number of women from getting breast cancer, but it will take 10 years of follow-up to see a real prevention," Powles said.

Barnett Kramer, deputy director of the National Cancer Institute in Bethesda, Md., said the British and Italian studies do not shake his confidence in the findings of the U.S. study.

"We are extremely confident, because of the number of women involved, that the data stands, and the chance that our results occurred by chance were 1 in 10,000," he said.

He said the inclusion of women taking hormone replacement therapy in the British study also skewed the results because it adds estrogen, which can blunt the effect of tamoxifen.

Powles countered that even discounting the women on hormone replacement therapy, there was no significant difference in the cancer rate.

In a separate commentary in The Lancet, Kathleen Pritchard of the University of Toronto in Canada said the differences in the European and U.S. findings may reflect the fact that more women participated in the American study, that they were older and that the risk factors taken into account were different.