Hormones May Increase Cancer Risk, Study Says
Long-term use of a popular hormone therapy given to millions of older women to reduce the symptoms of menopause and prevent osteoporosis may quadruple their risk of developing breast cancer, a startling new study by Swedish and U.S. researchers suggests.
The findings, announced Tuesday in Sweden and to be published Thursday in the New England Journal of Medicine, found that women who took a combination of estrogen and progestin for more than six years were 4.4 times more likely than others to develop cancer of the breast.
The study “could change the way we think about post-menopausal hormone replacement,” Dr. Elizabeth Barrett-Connor of UC San Diego wrote in an editorial accompanying the study. Yet she and others said the findings are too preliminary to recommend a change in practice.
A significant percentage of all menopausal and post-menopausal women--some experts estimate one-third to one-half--receive estrogen replacement therapy. Production of natural estrogen hormones in the ovaries slows down during and after menopause.
The hormone therapy is used in the short run to minimize symptoms of menopause, such as hot flashes, sweating and other physical changes. In the long run, physicians use it to prevent the bone-thinning, or osteoporosis, that afflicts many older women.
Combined Therapy
In the United States, most of those women also receive progestin, a synthetic form of the female hormone progesterone. Progestin is used to counteract an unintended side effect of estrogen therapy discovered in the 1970s--its tendency to increase a woman’s risk of uterine cancer.
“This article hits at the heart of our philosophy that patients should be on estrogen and progestin,” said Dr. Jonathan S. Berek, director of gynecologic oncology at UCLA School of Medicine. “This questions the assumption that it is entirely safe, at least from the standpoint of the breast.”
The researchers studied 23,244 Swedish women age 35 or older who received various types of estrogen therapy. They then compared their rate of new cases of breast cancer to that of women in the same region who did not receive estrogen replacement.
The women on estrogen were on average 10% more likely to come down with breast cancer during the six-year study, the researchers found. The longer the women received estrogen, the greater their risk: women who were on estrogen nine years or more were 70% more likely to come down with breast cancer.
One particularly potent form of estrogen, called estradiol, which is not used widely the United States, was associated with a nearly 200% increase in risk. Other types of estrogens appeared to result in no increased risk of breast cancer.
Popular Treatment
Experts said Tuesday that the study’s most provocative finding was the fourfold increase in risk of breast cancer among women on combined estrogen and progestin therapy, the approach that has grown increasingly popular in the United States in the past 10 years and is the therapy of choice for women who have not had a hysterectomy.
“This paper says (the addition of progestin) may actually increase the amount of breast cancer you get from estrogen alone,” said Dr. Brian E. Henderson, a cancer specialist at USC. “You don’t want that effect. But it’s a worry we’ve had.”
Experts stressed that the Swedish findings must be confirmed in further studies before any change in medical practice can be recommended. They said any suspected drawbacks of the combination therapy must be weighed against its proven benefits.
For example, estrogen therapy is believed by some to reduce a woman’s risk of heart disease and stroke, in addition to its other benefits. Some also noted that progestin is being prescribed in lower and lower doses, perhaps reducing any risk.
“To a woman on estrogen replacement therapy, the message we all want her to get is ‘Don’t change what you’re doing,’ ” said Henderson. “ ‘You’re doing the right thing. We’re just trying to understand better how to maximize the benefit to you.’ ”
Risks and Benefits
Barrett-Connor said the study “might draw attention to how little we really know about the best possible combinations or single drugs that would have the best risk-benefit ratio. We really don’t have that information yet and we’re scrambling to get it.”
Dr. S. B. Gusberg, a past president of the American Cancer Society, said it may prove necessary to make estrogen therapy a short-term, rather than a long-term therapy. Studies suggest there is no added risk in taking the hormones up to five years, he said.
“You can take the combination for relatively short periods . . . up to four or five years,” said Gusberg, an emeritus professor of gynecology at Mt. Sinai School of Medicine in New York. “The message is, don’t take any powerful substance, like estrogenic hormone, forever.”
The authors were Dr. Leif Bergvist and others at University Hospital in Uppsala, Sweden. Also involved were researchers from the U.S. National Cancer Institute.
