Six years after landmark research uncovered breast cancer risk in the nation’s most popular menopause treatment, two new Stanford University analyses show that using hormone replacement therapy long-term poses a far greater risk of cancer than previously thought.
The research concludes that a woman who stays on the therapy for at least five years doubles her risk of breast cancer every year. This 200 percent elevated risk is much greater than the 27 percent risk described in the landmark 2002 Women’s Health Initiative report, the first study to establish a link.
But the new studies, which tracked women in the original research, also offer good news: No risk was established when women took it less than five years. And for women who took it longer, risks dropped when they stopped treatment.
Despite the 2002 results, millions of women have continued to use hormone replacement therapy to ease symptoms such as severe hot flashes. Some continued due to lack of good alternatives; others were not aware of the cancer risks, despite the wide publicity drawn by the earlier study.
“I would encourage women to try and make it through menopause without starting hormone treatment,” said to Marcia Stefanick, professor of medicine at Stanford University School of Medicine and a co-author of both the 2002 and new study.
“If you do start, go for the lowest dosage and the shortest duration,” she said. The paper is published in Wednesday’s New
England Journal of Medicine.
The latest studies follow the Women’s Health Initiative report, which found that postmenopausal women taking an estrogen plus progestin combination — in a pill called PremPro, made by Wyeth Corp. — were at greater risk of breast cancer than women on placebo.
The finding was so dramatic that the study was abruptly halted. Use of hormone therapy plummeted in the United States, dropping from 60 million prescriptions in 2001 to 20 million in 2005, the latest figures available. Since then, breast cancer diagnoses have fallen, as well.
“It was a big seller — a very big seller. Then there was an enormous change,” said Cindy Pearson, executive director of the National Women’s Health Network in Washington D.C. “It was one of the biggest changes in prescribing habits for a drug commonly used by millions of healthy people.”
Stefanick hopes the new research puts to rest a raging debate over the cause of the nation’s declining rates of breast cancer. When cancer cases fell in the years following the release of the 2002 report, some physicians suggested that other factors, such as changes in mammographies, might explain the trend. But Stefanick studied mammogram usage, and ruled that out as a cause.
“It confirms that stopping hormones really does reduce cancer,” she said.
Pearson and other patient advocates worry that younger patients, just now experiencing menopause, may not have learned the lessons of the 2002 study. Even more worrisome, their doctors may not be educating them. A 2004 Stanford survey published in the journal Menopause found that only 3 in 10 women recalled anything about the study, and fewer than half were familiar with the pros and cons of hormone replacement therapy.
“There are still a fair number of doctors and women who depart from the science when they’re thinking about whether to take PremPro,” said Pearson.
Wyeth did not return requests for comment.
For the latest findings, Stefanick and her team followed the 15,000 women in the original study for an additional 2.5 years. In a second, they studied 41,449 women who had not been assigned treatment but took it voluntarily.
For both groups — which included many women in treatment for at least five years, and sometimes far longer — the risk of cancer was much more pronounced than suggested by previous data, she said. Furthermore, researchers found that as the number of women taking drugs declined, there was a corresponding drop in the number of breast cancer cases.
Women who cannot tolerate symptoms of menopause may try PremPro, said Stefanick. But she recommended using the lowest dosage possible and interrupting treatment after two to three years, to see if symptoms returned. Because menopause is a transitional phase, many women find they no longer need the drug.
“Don’t see it as something to take for the rest of your life,” she said.
The results do not apply to women taking estrogen alone. Although estrogen-only treatment has been linked to endometrial cancer, women who have had hysterectomies may benefit from treatment, she said.
With the link now firmly established, patient advocates urge scientists to start looking at other causes for a disease that kills about 40,000 American women a year.
“It’s proven. We don’t need any more research on this topic,” said Barbara Brenner, director of the San Francisco-based patient advocacy group Breast Cancer Action, “It’s time to study other things.”
Contact Lisa M. Krieger at
or (408) 920-5565.