Hormone Replacement Therapy and Breast Cancer Relapse
Breast cancer survivors who took hormone replacement therapy (HRT) to relieve menopausal symptoms had more than three times as many breast cancer recurrences as survivors who did not take HRT, a new study from Sweden has found. The study - which was stopped ahead of schedule because of these findings - was the first randomized clinical trial to examine the effect of HRT in women with breast cancer.
The Lancet, published online Feb. 3, 2004; in print Feb. 7, 2004 (see the journal abstract).
(Lancet. 2004 Feb 7;363(9407):453-5.)
Improved survival among women with breast cancer has meant that more breast cancer survivors are going through menopause, which for some women causes severe symptoms such as hot flashes, night sweats, and loss of sexual desire. For many years, HRT (usually a combination of the hormones estrogen and progestin) was widely prescribed to women to relieve these menopausal symptoms. It was also thought that HRT might reduce the risk of breast cancer, heart disease, and other conditions.
However, in July 2002, a large randomized clinical trial of estrogen and progestin in healthy postmenopausal women (part of the Women's Health Initiative) was stopped early when researchers found that women who took the hormones had an increased risk of developing breast cancer and heart disease. (For more information, see the collection of links at Menopausal Hormone Use.)
The U.S. Food and Drug Administration has since recommended that women discuss with their doctors whether the benefits of taking estrogen and progestin outweigh the risks and that, if used, the hormones should be taken "at the lowest doses for the shortest duration to reach treatment goals.”
The effects of HRT on women who had already had breast cancer had not been studied in a randomized controlled trial, considered the “gold standard” in medical research. Because more than half of breast cancers are fueled by estrogen, some researchers worried that use of the hormone could stimulate recurrence of the disease. However, studies that simply observed breast cancer survivors for several years concluded that the risk of cancer recurring in HRT users was low.
In 1997, Swedish researchers began a randomized trial to determine whether a two-year course of HRT for menopausal symptoms was safe for women who had been treated for breast cancer. A total of 434 study participants were randomly assigned to receive either HRT or non-hormonal treatment for their menopausal symptoms. The research team was led by Lars Holmberg, M.D., of University Hospital in Uppsala, Sweden.
The researchers intended to follow the women for a median of five years. However, after a median follow-up of just over two years, they found that 26 women in the HRT group - but only seven in the non-HRT group - had had a recurrence of breast cancer. They terminated the study, concluding that even short-term use of HRT posed an “unacceptably high risk” of breast cancer recurrence.
Note: Results from a longer period of follow-up confirmed these findings and were published in the April 2, 2008, Journal of the National Cancer Institute (see the journal abstract).
The study fell far short of its recruitment goal, enrolling just 434 women instead of 1,300 as originally planned. In addition, the study was not blinded or placebo-controlled, two characteristics that are generally considered to strengthen the findings of a clinical trial.
“In and of itself, this study would not be strong enough to provide conclusive evidence that breast cancer survivors should avoid HRT,” said JoAnne Zujewski, M.D., a medical oncologist who specializes in breast cancer at the National Institutes of Health Clinical Center in Bethesda, Maryland.
“However, these results are consistent with those of other studies, including the Women’s Health Initiative study,” Zujewski added. “As a practical matter, given what we already know about the serious risks and extremely limited benefits of HRT, these findings can be considered definitive.”
Zujewski’s comments are supported by an editorial accompanying the study report, which says that the “conclusion that even short-term use of hormone therapy poses an unacceptably high risk of breast cancer can now reasonably guide clinical practice for women with breast cancer.” The editorial is written by Rowan T. Chlebowski, M.D., of the Harbor-UCLA Research and Education Institute in Torrance, California, and Nananda Col, M.D. of Brigham and Women’s Hospital in Boston.
The study also demonstrates the importance of testing treatments in randomized clinical trials, Zujewski said. “You cannot draw definitive conclusions from observational studies. Definitive conclusions come from randomized studies.”
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