“In the aftermath of the WHI, consider estrogen patient by patient”
Janelle Yates, Senior Editor
Women who participated in the estrogen-progestin arm of the WHI and who were followed for approximately 11 years had an increased incidence of breast cancer—and those cancers were more likely to be advanced, with a higher risk of death. That is the finding of a new study led by Rowan T. Chlebowski, MD, PhD, of Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center in Torrance, Calif. The study was published in the October 20 issue of JAMA.
Chlebowski and colleagues analyzed data and report updated information on breast cancer incidence. For the first time, they also make information available on breast cancer mortality related to the use of combined hormone therapy in the WHI trial.
A total of 16,608 postmenopausal women 50 to 79 years old who had no history of hysterectomy were randomized, in 40 US clinical centers, to combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo. After the original trial completion date (March 31, 2005), repeat consent was required for continued follow-up for breast cancer incidence and was obtained from 12,788 (83%) of the surviving participants.
In intention-to-treat analyses including all randomized participants (except for those who failed to consent to additional follow-up), researchers found that estrogen plus progestin increased the incidence of invasive breast cancer to a greater extent than placebo did (385 cases [0.42% per year] vs. 293 cases [0.34% per year], respectively). A significantly larger percentage of women in the combined hormone therapy group had breast cancers with positive lymph nodes, compared with women in the placebo group (81 [23.7%] vs. 43 [16.2%], respectively).
“More women died of breast cancer in the combined hormone therapy group compared with the placebo group (25 deaths [0.03% per year] vs. 12 deaths [0.01% per year]), representing 2.6 vs. 1.3 deaths per 10,000 women per year, respectively,” the investigators write. “Consideration of all-cause mortality after breast cancer diagnosis provided similar results; among women in the combined hormone therapy group, there were 51 deaths (0.05% per year) compared with 31 deaths (0.03% per year) among women in the placebo group, representing 5.3 vs. 3.4 deaths per 10,000 women per year, respectively.
“With some exceptions, the preponderance of observational studies have associated combined hormone therapy use with an increase in breast cancers that have favorable characteristics, lower stage, and longer survival compared with breast cancers diagnosed in nonusers of hormone therapy,” Chlebowski and colleagues write. However, in the WHI randomized trial, combined hormone therapy increased breast cancer risk and interfered with breast cancer detection, leading to cancers being diagnosed at more advanced stages.
“Now, with longer follow-up results available, there remains a cumulative, statistically significant increase in breast cancers in the combined hormone therapy group, and the cancers more commonly had lymph node involvement. The observed adverse influence on breast cancer mortality of combined hormone therapy can reasonably be explained by the influence on breast cancer incidence and stage.
“Following the initial report of results from the WHI trial,” the researchers note, “a substantial decrease in breast cancer incidence occurred in the United States, which was attributed to the marked decrease in postmenopausal hormone therapy use that occurred after publication of the trial results. The adverse influence of estrogen plus progestin on breast cancer mortality suggests that a future reduction in breast cancer mortality in the United States may be anticipated as well.”
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