JAMA Logo Hormone therapy may be beneficial for postmenopausal women, but it also has certain disadvantages. According to a recent study, postmenopausal women employing estrogen plus progestin probably face heightened incidence of more advanced breast cancers along with a significant risk of deaths due to this disease. The findings can help reduce breast cancer mortality rates.

The Women’s Health Initiative (WHI) randomized, placebo-controlled trial of estrogen plus progestin was commenced after an average intervention time of 5.6 years and an average follow-up of 7.9 years. Breast cancer incidence was supposedly elevated in women receiving combined hormone therapy. Data and report updated information on breast cancer incidence of the disease’s mortality related to combined hormone therapy use in the WHI trial was thoroughly scrutinized by the authors. 16,608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 U.S. clinical centers were encompassed in the study. Participants were randomly selected to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill.

Scientists quote, “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. 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.”

When the original trial was completed on March 31, 2005, the follow-up for breast cancer incidence was initiated on 12,788 surviving participants forming 83 percent. In intention-to-treat analyses, incidence of invasive breast cancer was reported by 385 cases representing 0.42 percent per year from the estrogen plus progestin and 293 cases presenting 0.34 percent annually in the placebo group. Rowan T. Chlebowski, M.D., Ph.D., of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, Calif., and colleagues noted that 81 forming 23.7 percent of the combined hormone therapy group and 43 representing 16.2 percent in the placebo group had breast cancers with positive lymph nodes.

Investigators highlight, “Following the initial report of results from the WHI trial, 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.”

25 deaths presenting 0.03 percent each year were registered in the combined hormone therapy group and 12 death forming 0.01 percent per year by the placebo group. As per the statistics achieved, among every 10,000 women annually, 2.6 deaths occurred in the combined hormone therapy group and 1.3 in the placebo group. Even after taking into consideration all-cause mortality after breast cancer diagnosis, similar results appeared. Per year 51 deaths representing 0.05 percent were noted in the combined hormone therapy group and 31 comprising 0.03 percent in the placebo group. So in every 10,000 women per year, 5.3 deaths in the combined hormone therapy group and 3.4 in the placebo group were seemingly observed.

The study is published in the October 20 issue of JAMA.