Quitting combination hormone therapy rapidly lowers a woman's risk of breast cancer, according to a new analysis of the massive Women's Health Initiative clinical trial. What's more, taking Prempro, an estrogen-progestin drug, for five years doubled a woman's risk of breast cancer. The paper, in The New England Journal of Medicine, was co-authored by researchers...

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Breast-cancer rates fell steeply and swiftly among postmenopausal women who quit combination hormones in 2002 after warnings about their potential hazards.

That’s according to the latest follow-up of a landmark federal study that overturned a decades-long medical convention about hormone therapy.

Investigators from Seattle’s Fred Hutchinson Cancer Research Center and elsewhere also found that a woman’s risk of developing breast cancer doubled after taking estrogen plus progestin for five years — a higher number than previously thought and the strongest indication yet that the cancer risks escalate the longer a woman stays on combination hormones.

The findings, published Wednesday in The New England Journal of Medicine, likely will heighten the dilemma for millions of women in search of postmenopausal relief.

Many doctors continue to prescribe hormones to ease menopause symptoms, albeit in smaller doses and for shorter duration than before.

Dr. Rowan Chlebowski, the study’s lead author and a chief investigator at Los Angeles Biomedical Research Institute, said estrogen-progestin appears to act as a growth factor in the body, stimulating cancer cells. But the effect seems to dissipate quickly once hormones are withdrawn, he said.

An oncologist, Chlebowski said the findings should help allay lingering skepticism among some physicians about hormone therapy’s role in triggering breast cancer.

Physicians should regularly review whether women should stay on hormone therapy for more than three or so years, he said, — something he suspects not all do.

Health initiative

The study is the latest follow-up to the Women’s Health Initiative, which enlisted more than 16,000 women and randomly assigned some to take Prempro, an estrogen-progestin drug.

Researchers halted the clinical trial three years early, in July 2002, after concluding that Prempro posed unacceptable risks of breast cancer, heart attack, stroke and blood clots.

The decision stunned physicians, who for two decades had prescribed hormones for postmenopausal women in the belief they protected against heart disease and brittle bones.

Hormone prescriptions around the nation fell dramatically — from 60 million in 2001 to 20 million in 2005. Since then, the number of breast-cancer cases in the United States has dropped by about 20,000 annually.

The new analysis “suggests that could be due to the remarkable cessation of hormone therapy” among U.S. women this decade, said Ross Prentice, a biostatistician at Fred Hutchinson and one of the paper’s co-authors.

Within a year of the women quitting Prempro, breast-cancer diagnoses among them fell by 28 percent, to 1 in 231, compared with 1 in 166 for women who had stayed on the hormones for five years.

The rapidity of that reversal was unexpected, Prentice said. Within a year of quitting hormones, a woman’s risk of breast cancer subsided to a rate of nearly 1 in 217 for women who’d taken Prempro for less than three years.

Preliminary estimates, Prentice said, indicate that 12,000 of the 20,000 fewer breast-cancer cases may be attributable to the decline in Prempro use.

The findings do not apply to women who take estrogen only, or who take different types of progesterone than is used in Prempro.

Altered perspective

Dr. Jane Dimer, a gynecologist with Seattle’s Group Health Cooperative, said the original findings of the Women’s Health Initiative have changed the way she and her colleagues talk about menopause.

Doctors previously used the term hormone-replacement therapy (HRT), which carried the connotation that menopausal women were missing something essential.

HRT “used to roll off our tongues,” Dimer said. “Now the idea of ‘replacement’ is out of vogue.”

When hormone therapy is warranted, Dimer said, she customizes treatment by adjusting dosage or prescribing separate pills for estrogen and progesterone.

She also tries different hormones, such as norethindrone, a type of progesterone more commonly used in Europe.

“In the end, it’s really the patient’s decision about what kind and how long” she stays on hormones, Dimer said.

Dimer said she is not wholly convinced that hormone therapy is a direct culprit behind many women’s breast cancers. She noted that the subjects in the Women’s Health Initiative’s clinical trial were older, 64 on average, compared with about 51 for typical women who start hormone therapy.

“I still think there is an awful lot more about why breast cancer is so common in America,” Dimer said.

Kyung Song: 206-464-2423 or ksong@seattletimes.com