Estrogen Therapy Doesn't Cause Breast Cancer: Study

But treatment isn't risk-free, so women should consult their doctors, experts say

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By Amanda Gardner
HealthDay Reporter

TUESDAY, April 11, 2006 (HealthDay News) -- Estrogen therapy on its own does not increase the risk of breast cancer in postmenopausal women, an extensive new study has found.

The findings, from the Women's Health Initiative (WHI), stand in stark contrast to previous results from the estrogen-plus-progestin arm of the trial. That study was halted in 2002, three years ahead of schedule, when evidence showed a higher risk of not only breast cancer, but blood clots, stroke and heart attack.

While the new report found no evidence that estrogen therapy causes breast cancer, other research has found the therapy can cause blood clots in postmenopausal women, potentially leading to cardiovascular problems. So, women need to consult with their doctors to weigh the benefits and risks of estrogen therapy, experts said.

"People have to stop thinking all hormones are the same," said Marcia L. Stefanick, professor of medicine at Stanford University's Stanford Prevention Research Center and chairwoman of the WHI steering committee and executive committee. "There is no contradiction."

"The current findings are good news for women on estrogen but it doesn't help women on the combined therapy," Stefanick added.

The new findings appear in the April 12 issue of the Journal of the American Medical Association.

Outside experts also considered the new finding good news for women struggling with menopausal symptoms, which can include hot flashes, vaginal dryness and loss of energy.

"It does provide reassurance to patients taking estrogen that it might not be as bad as everyone assumed," said Dr. Jennifer Wu, an obstetrician/gynecologist with Lenox Hill Hospital in New York City. "Many patients have such severe symptoms that they really don't want to stop taking their estrogen."

Added Dr. Hugh Taylor, associate professor of obstetrics and gynecology at Yale University School of Medicine: "This study is great news for women, especially those entering menopause. We have seen confusing and conflicting information that has led to exaggerated and unfounded fears of estrogen. I think the rollercoaster ride is over."

Taylor spoke at an April 7 teleconference sponsored by Wyeth Pharmaceuticals, which makes Premarin and Prempro, hormone therapies intended to mollify symptoms of menopause.

The Women's Health Initiative is a 15-year-long examination of the causes and prevention of diseases affecting older women. So far, the research has produced a complicated picture of the risks and benefits related to hormone therapy.

An earlier set of WHI results found that estrogen therapy did not diminish or increase the risk for heart disease, while leaving open the possibility that it might reduce the risk in women aged 50 to 59.

The estrogen-only portion of the trial -- the subject of the new findings -- was also stopped early (in 2004) because of an increased risk of stroke and blood clots and no reduction in the risk of coronary heart disease. Preliminary data showed no risk of breast cancer; the new findings represent the final data.

For this study, the researchers analyzed data on 10,739 postmenopausal women aged 50 to 79 at 40 clinical centers throughout the United States. The participants were randomly chosen to receive either estrogen or a placebo and underwent mammography screenings and clinical breast exams at the beginning of the study and annually thereafter. The data was collected between 1993 and 1998.

All the women in the study had undergone a hysterectomy. Estrogen alone cannot be given to women with a uterus because of an increased risk of uterine cancer. Instead, these women take estrogen plus progestin to mitigate the risk. "The addition of progestin is to protect the uterus against the estrogen, but if you don't have a uterus you can take just estrogen," Stefanick explained.

After an annual follow-up of 7.1 years, women in the estrogen group had a slightly and statistically non-significant reduction in their risk for invasive breast cancer (20 percent lower) and total breast cancer (18 percent lower).

When they were diagnosed with breast cancer, however, women in the estrogen group tended to have larger tumors that were more likely to have spread to the lymph nodes. This suggests that estrogen may lower the risk of smaller cancers but not larger ones, the researchers said.

Women who had a low risk of breast cancer -- such as no family history or no benign breast disease -- had fewer breast cancers while on estrogen, while those with a higher risk had more breast cancers.

Overall, though, the evidence seems to indicate that estrogen therapy does not contribute to a higher risk of breast cancer.

"These data are pretty good evidence that estrogen therapy is relatively safe for breast cancer," Stefanick said.

The true existence of breast cancer among the study participants still needs to be double-checked, cautioned Dr. William T. Creasman, J. Marion Sims professor of obstetrics and gynecology at the Medical University of South Carolina. Creasman also spoke at the Wyeth news conference. "We don't know if these are all breast cancers," he said. "We're taking the word of the individuals who reviewed the slides initially and that, we know, has a margin of error."

But other factors, such as the increased risk for blood clotting, still need to be taken into account when prescribing hormone therapy.

In fact, a study published Monday in the Archives of Internal Medicine found that estrogen therapy appears to increase the risk of blood clots in the veins of postmenopausal women who have had their uterus removed.

"The paradigm of treating most women who are symptomatic with the lowest effective dose for the shortest amount of time makes sense," Taylor said.

In a prepared statement, Dr. Joseph Sanfilippo, president of the American Society for Reproductive Medicine, cautioned that "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."

More information

Visit the National Heart, Lung, and Blood Institute for more on the Women's Health Initiative.

Marcia L. Stefanick, Ph.D., professor of medicine, Stanford Prevention Research Center, Stanford University, Palo Alto, Calif; Jennifer Wu, M.D., obstetrician/gynecologist, Lenox Hill Hospital, New York City; April 7, 2006, teleconference with Hugh Taylor, M.D., associate professor of obstetrics and gynecology, Yale University School of Medicine, New Haven, Conn., and William T. Creasman, M.D., J. Marion Sims professor of obstetrics and gynecology, Medical University of South Carolina, Charleston; April 12, 2006, Journal of the American Medical Association

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