Study Links Breast Cancer, Hormone Use

One of the largest studies examining the association between hormone replacement therapy and breast cancer has concluded that the standard version of the therapy--a combination of the hormones estrogen and progestin--substantially increases a woman’s risk of developing breast cancer if taken for many years.

For each year of combined therapy, a woman’s risk of breast cancer was found to increase by 8% compared with a 1% increase in women taking estrogen alone, according to the research from the National Cancer Institute.

The risk, which does not seem to apply to overweight women, accumulates the longer a woman adheres to hormone therapy. For example, a woman on combined therapy for 10 years would increase her risk of breast cancer by 80% in the 10th year of use, according to the new data.

The study, published in today’s Journal of the American Medical Assn., should persuade certain groups of women, such as those planning only a short course of hormone therapy, to avoid progestin, said Dr. Walter C. Willett, a Harvard epidemiologist who wrote an editorial accompanying the paper. Other women should weigh their options carefully, he added, including diet and lifestyle changes.

“I think this study is particularly important because it adds to a body of evidence that the addition of progestin to hormone replacement therapy increases the risk of breast cancer,” Willett said in an interview. “Hormone therapy applies to a large percentage of women. It’s a very common therapy.”

American women, in general, have a 1 in 9 chance of developing the disease over a lifetime. The added risk from long-term hormone use, he added, “is a big . . . risk, given that breast cancer is pretty common to begin with.”

According to the authors of the study, led by Catherine Schairer of the institute, breast cancer risk did not increase among heavy women taking either combined or estrogen-only therapy. The increased cancer risk was only found in women with a body mass index considered “lean.”

“Our results, as well as those of others, suggest that in weighing the risks and benefits of menopausal [hormone replacement therapy], it is important to consider the type of hormone regimen as well as individual characteristics of the woman, such as body mass index,” Schairer wrote in the paper.

The study examined data on 46,355 post-menopausal women who were part of the Breast Cancer Detection Demonstration Project from 1973 to 1980 and then were followed for up to 15 years. The women were sent questionnaires in which they were asked about their use of hormone therapy and whether they had developed breast cancer. Among the participants, 2,082 were diagnosed with the disease.

The question of whether to take hormones has been among the most complicated issues in preventive health care. At menopause, the body ceases to produce adequate quantities of estrogen, which can lead to a number of problems, including hot flashes and vaginal dryness.

Moreover, the loss of estrogen at menopause elevates the risk of the degenerative bone disease osteoporosis, strongly appears to increase the risk of heart disease and may even contribute to dementia in aging.

Therapy Combines Estrogen, Progestin

Estrogen therapy is widely believed to offset those risks. However, doctors routinely prescribe adding progestin to the estrogen therapy because estrogen alone increases the risk of uterine cancer. Adding progestin allows the lining of the uterus to shed through menstruation, thereby reducing the risk of uterine cancer.

What has remained unclear is the effect of the hormones on breast cancer risk, said Dr. William Creasman, chairman of obstetrics and gynecology at the Medical University of South Carolina, in Charleston, and an authority on hormone therapy.

“This study has one thing that is new: It looks at estrogen plus progestin. As for whether this data is important or not, I think we need a whole lot more data before we can say,” he said.

Creasman said there were several drawbacks in the study, including the question of whether the women could accurately recall their hormone use.

For example, he said, “People who develop breast cancer are much more likely to remember whether they took hormones compared to women who don’t develop the disease.”

In addition, the women in the study may not resemble women today, Creasman added, because many women now take lower doses of progestin than was used during the follow-up years of the study (1979 through 1995).

The study also does not resolve the question of whether hormone therapy is really riskier for lean women. According to Willett, heavier women already have a significantly higher risk of breast cancer because their bodies produce more estrogen. “It has been known for quite a while that adding estrogens causes the biggest increased risk of breast cancer in lean women,” he said.

However, based on the study and others like it, Willett said certain recommendations can be made, such as bypassing progestin during short-term therapy. The study confirmed earlier observations that the extra risk of developing breast cancer declines quickly once the hormone regimen is stopped.

“Using hormone therapy for a year or two at the time of menopause and for symptom relief is not an important issue,” Willett said. “But in that case, when you are using hormones for a couple of years, there is no reason to use combination therapy. These women can use estrogen alone.”

The study also supports the advice that women without a uterus should probably avoid taking progestin, Willett said.

Exercise, Diet Are Alternative to Drugs

All post-menopausal women should consider whether they might be able to lower their risks of osteoporosis and heart disease by means other than hormone therapy, he added.

Diligent attention to nutrition and exercise can achieve the same goals, he said.

Women should also pay close attention to the development of a new class of medications, called selective estrogen receptor modulators (which include the drugs raloxifene and tamoxifen), which may prove to offer the benefits of hormone therapy without the risks, Willett said.

“This is complex, and there is no single answer for all women,” he said. “Women need to discuss this with their physicians.”

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Pros and Cons of Hormone Therapy

Post-menopausal women must weigh the risks and benefits of taking hormone therapy.

RISKS

* Apparently increases risk of breast cancer in lean women who are current or recent users, especially those taking estrogen and progestin.

* Increases risk of uterine cancer in women who are taking estrogen alone.

BENEFITS

* Alleviates symptoms of menopause, including hot flashes and vaginal dryness.

* Reduces the risk of osteoporosis.

* Strong possibility that it reduces risk of heart disease.

* Some evidence that it plays protective role against dementia.

Sources: Journal of the American Medical Assn., Vol. 283, No.4; The Lancet, Vol. 354, No. 9173.