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Study: Estrogen Protects Some from Breast Cancer

A new analysis of the large-scale Women's Health Initiative Estrogen-Alone trial offers some reassurance to women who take estrogen following a hysterectomy. The study found that postmenopausal women treated with estrogen therapy for seven years did not experience an increased risk of breast cancer. The findings are published in the Journal of the American Medical Association.

The findings do not overturn prior thinking about hormones. Rather they suggest that it's the combination of estrogen and a second hormone, progestin, needed to protect the uterus that have been shown to increase the risk of breast cancer. This risk seems to disappear when women take estrogen alone.

"There's been a lot of confusion about hormones" says Marcia Stefanick, professor of obstetrics and gynecology at Stanford University. "Many women heard all the news back in July 2002 about estrogen and progestin therapies increasing breast cancer," says Stefanick. "The message that women got was that hormones increase breast cancer. People didn't distinguish between estrogen-alone therapy and a combination therapy of estrogen and progestin. Now we see that estrogen-alone therapy from the Women’s Health Initiative trial does not increase breast cancer."

The Women's Health Initiative Estrogen-Alone trial enrolled 10,739 women, ages 50-79. The women were divided into two groups. One group took a daily dose of estrogen therapy known as CEE, which is made of conjugated horse estrogens. The other group took a placebo pill. The trial was halted earlier than planned because of an increased rate of strokes and no reduction in the risk of coronary heart disease among the women.

Some of the Women's Health Initiative (WHI) researchers expected to find an elevated risk of breast cancer as well, since previous studies had found some evidence that estrogen increases the risk of breast cancer. Also, a separate arm of the WHI had found that women taking a combination estrogen/progestin therapy did increase their risk of breast cancer. But researchers’ predictions were wrong.

"The finding that estrogen alone taken for seven years doesn't increase the risk of breast cancer is surprising" says JoAnn Manson, professor of medicine at Harvard Medical School.

The study suggests that estrogen-alone therapy seemed to offer some additional protection against breast cancer for women who had no family history of the disease. In groups of about 5,000 each, there were 129 cancers in the estrogen group and 161 cancers in the placebo group. Manson says what remains unclear is the mechanism.

Researchers also question whether the effect will hold up over a lifetime. "Would a longer duration of treatment with estrogen alone eventually lead to an increased risk of breast cancer? We need to look further into this issue because some women are taking hormone therapy for longer than seven years" says Manson.

The results of the new estrogen-alone study may be reassuring to some women. It's particularly applicable to women taking estrogen for a few years following a hysterectomy.

But Manson cautions the estrogen-only study results can't be generalized to the population at large. "The findings apply only to women who've had a hysterectomy," says Manson.

The reason is that women who still have a uterus need to take progestin when they're on hormones in order to protect against uterine cancer.

Some experts say a fresh approach is needed for all menopausal women. "I think we must rethink how we administer hormone therapy in this country", says Hugh Taylor, professor of obstetrics and gynecology at Yale University and a paid speaker for a hormone manufacturer. Taylor suggests one solution might be to find a better balance of estrogen and progestin.

"Perhaps we ought to think about going back to some of the cyclic regimens where progestin is used during just part of a woman's cycle or maybe we can use lower doses of progestin," Taylor says.

These options are being evaluated.

"The latest findings reinforce the importance of the message we have always given about hormone therapy," says Joseph Sanfilippo, president of the American Society of Reproductive Medicine. "Women must make decisions about the use of hormone therapy in conjunction with their physician. Each woman is different and her symptoms and risk factors will be different.

The guidelines for using hormone therapies remain the same, says Janet Pregler, director of the Iris Cantor Women's Health Center at University of California, Los Angeles. "Hormone therapy should be used in the smallest possible dose," she says, "for the shortest period of time needed to control symptoms."

With this approach women can limit their risks of strokes and blood clots, which are elevated by the use of hormone therapy. including estrogen alone.

Copyright 2022 NPR. To see more, visit https://www.npr.org.

Allison Aubrey is a correspondent for NPR News, where her stories can be heard on Morning Edition and All Things Considered. She's also a contributor to the PBS NewsHour and is one of the hosts of NPR's Life Kit.