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Breast Cancer Risk Subsides After HRT

Advice: Take Combined HRT at Minimum Dosage for Less Than 5 Years

From the WebMD Archives

Dec. 2, 2002 -- There's more breast cancer-related evidence against the estrogen-progestin form of hormone replacement therapy. However, the latest study gives women some comfort -- that risk begins to dissipate six months after women stop taking it.

"The study confirms the findings of the Women's Health Initiative," that estrogen-progestin therapy increases a woman's risk of breast cancer, says lead author Linda K. Weiss, PhD, an epidemiologist and chief of the National Cancer Institute's cancer center branch.

"But our study also adds something -- that when one discontinues use, the risk dissipates," Weiss tells WebMD. "That's reassuring. I know that some women are worrying that once you've taken it for five years and more that you always have the risk."

Weiss' study appears in the December issue of Obstetrics and Gynecology. The study was funded by the National Institute of Child Health and Human Development, the National Cancer Institute, and the CDC.

The NIH-funded Women's Health Initiative (WHI) was the first large clinical trial to look at the risks and benefits of estrogen-progestin therapy, a popular combination for women who suffer from hot flashes, night sweats, sleeplessness, and vaginal dryness. When taken alone, however, estrogen increases a woman's risk of cancer of the uterine lining -- endometrial cancer. When progestin is combined with estrogen, that risk virtually disappears.

When the WHI study began showing that women who took estrogen plus synthetic progesterone developed more risks than benefits, the researchers stopped the trial. Amid their disappointment was confusion; women didn't know what was safe anymore.

In their study, Weiss and colleagues evaluated risks from various forms of hormone replacement therapy. They also questioned women who had been diagnosed with breast cancer about their hormone use and other potential risk factors for breast cancer. Those women were then compared with women who had not developed breast cancer.

They enrolled 3,823 postmenopausal women -- 1,870 had a history of breast cancer while 1,953 had not had breast cancer -- and found that women who had taken estrogen-progestin therapy continuously for five years or more were 1.54 times more likely to develop breast cancer than women their age who were not taking this form of hormone replacement. They did not find an increased risk of breast cancer in women who took estrogen alone.

However, six months after they quit taking continuous estrogen-progestin therapy, the women's risk of breast cancer began to return to normal. This was true for women who took HRT five years or longer before stopping.

Researchers also found that an alternate form of "sequential" hormone therapy -- which involves taking the hormones separately, on different days of the month -- did not seem to increase breast cancer risk. In this form of HRT, women take the hormone progestin for five to 14 days a month. However, earlier studies have suggested that this regimen may increase the risk of uterine cancer.

"It does appear that estrogen combined with progestin is a particularly dangerous combination when it comes to breast cancer," says JoAnn Manson, MD, principle investigator of the WHI.

Manson, who is chief of preventive medicine at Brigham and Women's Hospital in Boston, agreed to comment on Weiss' study for WebMD.

"We recommend that women avoid long-term use of estrogen plus progestin," Manson tells WebMD. "Estrogen-progestin use should be limited to treatment of severe hot flashes, to improve quality of life in the short term -- and it should be used in the lowest possible doses, for the shortest amount of time. There is very little increased risk of breast cancer with hormone use of less than five years."

Regarding sequential hormone therapy, "the jury is still out in terms of breast cancer risk and overall benefit-to-risk ratio," says Manson. "The evidence has just been too limited. There have been no large-scale, randomized clinical trials of it."

Thus far, the evidence -- as premature as it may be -- shows that sequential hormone therapy may be less hazardous in terms of breast cancer, she says. "I think if progestin is taken for at least 12 days per month, it's supposed to protect the uterus with no increased risk of breast cancer."

"It is premature to assume that it is safe in terms of breast cancer," she tells WebMD. "We need more research to assure women of that."

Her advice: "If women need the estrogen-progestin combination, it should only be for treatment of severe hot flashes that impair quality of life. The main point is to minimize duration and dose. Also, if a woman has a family history of breast cancer, it would be particularly prudent to avoid hormone replacement therapy."

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SOURCES: Obstetrics and Gynecology, December 2002 • Linda K. Weiss, PhD, epidemiologist, and chief of the National Cancer Institute's cancer center branch. • JoAnn Manson, MD, chief of preventive medicine, Brigham and Women's Hospital, Boston. -->
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