MONDAY, Feb. 2, 2004 (HealthDayNews) -- For the third time in less than two years, researchers have halted a hormone therapy trial because the drugs posed unacceptably high breast cancer risks to women.
The latest trial, based in Sweden, was the first randomized study to look at the effects of hormone replacement therapy (HRT) on women who have had breast cancer. It was halted early because the risks of a recurrence of cancer were judged to be too great.
The finding prompted the head of the American Cancer Society to say it would be "unwise" to prescribe HRT to women with a history of breast cancer.
The Swedish study was originally scheduled to enroll at least 1,300 women and follow them for five years. The trial was stopped on Dec. 17, 2003, after following 345 women for about two years.
Twenty-six women in the HRT group and seven in the non-HRT group had a recurrence of breast cancer while they were receiving hormones.
"That's a substantial absolute risk," says lead investigator Dr. Lars Holmberg, a professor of clinical cancer epidemiology at the Regional Oncologic Centre of University Hospital in Uppsala, Sweden. "Most of us on the steering committee were prepared that, despite earlier studies, we might see a slightly increased risk but that the risk-benefit ratio still would be reasonable. So this was to us a surprise and also a very worrying result."
The finding will appear in the form of a research letter in the online edition of The Lancet on Feb. 3 and in the Feb. 7 print edition of the journal.
A concurrent study in Stockholm did not find a higher risk of cancer recurrence. But because a pooled analysis of the trials found an increased overall risk, that trial was also terminated. The results are not yet in on a third study, this one being conducted in the United Kingdom.
The latest announcements come on the heels of the early endings of two other high-profile HRT studies. In July 2002, the hormone therapy arm of the U.S.-based Women's Health Initiative (WHI) was halted when women taking hormones were found to have higher risks of coronary heart disease, stroke, blood clots and breast cancer. In October of the same year, the Women's International Study of Long Duration Oestrogen after Menopause (WISDOM), a British trial evaluating hormone therapy, was also stopped after finding elevated risks of breast cancer.
The results of the Swedish study have some doctors reevaluating their views on HRT.
Dr. Harmon J. Eyre, chief medical officer of the American Cancer Society, says in a statement: "Many women experience menopausal symptoms after treatment for breast cancer, some because they stopped using HRT, some as a result of chemotherapy and others as a natural part of aging. In the past, some doctors have offered HRT to selected breast cancer survivors who suffered from severe menopausal symptoms because a handful of small, preliminary studies had failed to show a risk."
"This study will no doubt change that," he adds. "It is large enough and clear enough to show that HRT appears to increase the chance of a new or recurring breast cancer. Because of that, offering HRT to women with a history of breast cancer would be unwise."
Dr. Steven Goldstein, a professor of obstetrics and gynecology at New York University School of Medicine in New York City, says the findings are "very, very significant. It's big news."
Many clinicians had felt HRT was safe for breast cancer survivors because observational studies, which are less stringent than randomized studies, had found no risk or only a slightly elevated risk, Holmberg says.
The halted Swedish study began recruiting in 1997. Women were randomized either to receive HRT or not to receive HRT. Participants in both groups were similar in age and other characteristics, although they might have varied in whether they had estrogen-receptor positive or negative cancers, the study authors write.
When results were compiled after about two years of follow-up, women in the HRT group were found to have a three-and-a-half times greater risk of having a recurrence of breast cancer than women in the non-HRT arm of the trial. The absolute risk of having a recurrence was 7.5 percent in the HRT group and 2 percent in the non-HRT group.
In addition to breast cancer, eight women in the HRT group and four in the non-HRT group experienced other serious health problems such as blood clots.
"I had been telling those patients going through menopausal transition that there is some data suggesting they can safely take HRT. This study suggests that is not true," Goldstein says.
Will he stop recommending hormone therapy to his patients who have had breast cancer?
"We still have to take this one pace at a time," Goldstein said. "If you have a 51-year-old woman nine years after her breast cancer with negative nodes who is absolutely beside herself [with menopausal symptoms], we may still decide on short-term therapy."
Holmberg adds: "I don't think this is the final word because our estimate is imprecise because it's so few women and the long-term results might be different."
Still, he notes, this is what doctors have to guide them for the foreseeable future.
More information
Get more on hormone therapy from the National Women's Health Information Center or the American College of Obstetricians and Gynecologists.
