Estrogen Alone Does Not Boost Risk of Breast Cancer

By Rob Stein
Washington Post Staff Writer
Wednesday, April 12, 2006

Taking estrogen alone does not increase the risk of breast cancer in menopausal women, according to a large federal study that offers reassurance to millions of women using the hormone to quell hot flashes and other symptoms.

The seven-year study of more than 10,000 women, the biggest, best-designed study to examine the risks of hormone therapy, found no evidence that estrogen alone increased the danger of developing the common malignancy, and produced evidence it may protect some women against the tumors. Earlier research had indicated the hormone raised the risk.

The findings apply only to women who can safely take estrogen alone because they have undergone a hysterectomy, but they are the largest group of hormone users -- about 3.5 million of the estimated 4.4 million American women using some form of hormone therapy.

Experts cautioned that no one should take estrogen alone to reduce their risk for breast cancer because the hormone carries other potential dangers. Women should still use the lowest possible dose of hormone therapy for the shortest possible time, they said. But the findings help alleviate a major concern about using estrogen for short-term relief of menopausal symptoms, they said.

"The jury is now in: Estrogen does not increase the risk for breast cancer, which is what most women thinking about using the hormone worry about," said Marcia L. Stefanick of Stanford University, who led the analysis being published today in the Journal of the American Medical Association.

The findings answer one of the major lingering questions in the long, confusing history of hormone use by menopausal women. For years, doctors encouraged women to take hormones in the belief it would protect their hearts, bones and possibly their mental functioning, along with alleviating the hot flashes, mood swings and other symptoms of menopause.

Doctors and women were shocked in 2002 when the federally funded Women's Health Initiative, the largest study ever conducted of women's health issues, found that estrogen and progestin not only were not protective but actually increased the risk of heart attacks, strokes, blood clots and possibly breast cancer, prompting millions to stop taking the hormones. Estrogen does protect bones, but it also appears to increase the risk of memory problems.

Since then, many women have begun using hormones again for short periods to help them get through menopause, despite continuing concerns about the impact on breast cancer. The disease strikes more than 211,000 women each year and kills more than 40,000, making it the most common cancer and second most common cause of death from cancer in women.

The new findings come from a second part of the Women's Health Initiative that involved women who were taking estrogen alone. Because taking estrogen alone increases the risk of uterine cancer, women who have not had their uterus removed must take a combination of two hormones, estrogen and progestin, to neutralize that risk. The estrogen-only part of the study was stopped in 2004 when researchers found that the hormone increased the risk of stroke and blood clots and provided no protection against heart attacks, just as the combination hormones did.

Although that part of the study had not found any increased risk of breast cancer at that point, the data were too preliminary to reach any firm conclusions. The new findings come from a final analysis of data from 40 centers on 10,739 women, ages 50 to 79, who took estrogen or a placebo for about seven years.

Not only was there no overall increased breast cancer risk among the women taking estrogen, the researchers found, but also there appeared to be somewhat fewer breast cancers among those taking the hormone -- 28 per 10,000 vs. 34 per 10,000 in the placebo group.

That difference may have been the result of chance, but further analysis of the data revealed a statistically strong reduced risk among some women: those who were already at low risk because they had no family history of breast cancer, benign breast disease or other reasons. The hormone appeared to reduce the risk primarily of smaller tumors that occur in the milk ducts. Women taking estrogen, however, did tend to have more abnormal mammograms, which resulted in more biopsies.

Although the hormone does increase the risk of stroke and blood clots, the findings are particularly reassuring for younger menopausal women, for whom the risk of strokes is low and the fears of breast cancer are high, experts said.

"It's very reassuring," said Isaac Schiff of the Massachusetts General Hospital in Boston, who chairs the task force on hormones of the American College of Obstetricians and Gynecologists. "For these women, who tend to need estrogen the most, they can be reassured that there is not increased risk for breast cancer."

The findings suggest that it is progestin, not estrogen, or perhaps the combination of the two, that increases the risk of breast cancer.

"Progestin is definitely a top suspect," Stefanick said.

The risk of blood clots is also lower among women taking estrogen alone, compared with taking estrogen and progestin, said Jacques Rossouw of the National, Heart Lung and Blood Institute, which runs the Women's Health Initiative.

"It's definitely beginning to look like it's the progestin component," Rossouw said. "There's just too many things piling up."

Rossouw and others cautioned, however, that women will need to be followed for a longer period to fully assess the risk of breast cancer from estrogen alone.

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