| Breast cancer risk rapidly drops after stopping hormone therapy
By Reuters Health February 5, 2009 |
The results of the Women's Health Initiative (WHI) trial released in 2002 linked use of estrogen plus progestin with increased breast cancer risk in postmenopausal women. Subsequently, use of this therapy in the U.S. decreased substantially accompanied by a drop in breast cancer rates. Whether the two trends were causally related, however, was unclear.
In fact, it was suspected that changes in the frequency of mammographic screening may have accounted for the apparent drop in breast cancer incidence.
To investigate, Dr. Marcia Stefanick, from Stanford University School of Medicine, California, and colleagues analyzed follow-up data from the WHI trial. Included in the postintervention phase of the trial were 7,854 women who had received conjugated equine estrogens (0.625 mg) plus medroxyprogesterone (2.5 mg) daily and 7,533 given placebo.
In the two years prior to the intervention phase of the study, fewer breast cancer diagnoses were seen in the combined hormone therapy group than in the placebo group. During the 5.6 years of intervention, however, the risk of breast cancer was 26% higher in the hormone therapy group.
After stopping hormone therapy, the risk of breast cancer fell rapidly. The annualized incidence decreased 43% within one year, and by two years it was essentially the same as in the placebo group.
Moreover, during this period, "differences in the frequency of mammography between the two groups were unchanged."
Overall, "This is very strong evidence that estrogen plus progestin causes breast cancer," Stefanick said in a statement. "You start women on hormones and within five years, their risk for breast cancer is clearly elevated. You stop the hormones and within one year, their risk is essentially back to normal. It's reasonably convincing cause-and-effect data."
Last Updated: 2009-02-04 17:00:12 -0400 (Reuters Health)
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N Engl J Med 2009;360:573-587
ABSTRACT
Background Following the release of the 2002 report of the Women's Health Initiative (WHI) trial of estrogen plus progestin, the use of menopausal hormone therapy in the United States decreased substantially. Subsequently, the incidence of breast cancer also dropped, suggesting a cause-and-effect relation between hormone treatment and breast cancer. However, the cause of this decrease remains controversial.
Methods We analyzed the results of the WHI randomized clinical trial — in which one study group received 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily and another group received placebo — and examined temporal trends in breast-cancer diagnoses in the WHI observational-study cohort. Risk factors for breast cancer, frequency of mammography, and time-specific incidence of breast cancer were assessed in relation to combined hormone use.
Results In the clinical trial, there were fewer breast-cancer diagnoses in the group receiving estrogen plus progestin than in the placebo group in the initial 2 years of the study, but the number of diagnoses increased over the course of the 5.6-year intervention period. The elevated risk decreased rapidly after both groups stopped taking the study pills, despite a similar frequency of mammography. In the observational study, the incidence of breast cancer was initially about two times as high in the group receiving menopausal hormones as in the placebo group, but this difference in incidence decreased rapidly in about 2 years, coinciding with year-to-year reductions in combined hormone use. During this period, differences in the frequency of mammography between the two groups were unchanged.
Conclusions The increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography.
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