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."
N Engl J Med 2009;360:573-587.
Last Updated: 2009-02-04 17:00:12 -0400 (Reuters Health)
