Incidence and mortality data from WHI

In 2002, the Women's Health Initiative (WHI) study was stopped early after 5.6 years when data showed that combination estrogen and progesterone therapy increased the risk of breast cancer. Mortality data had never been reported from WHI, however, and other studies have suggested that hormone therapy-associated breast cancers might have a more favorable prognosis than other breast cancers. A new analysis of WHI data dispels that notion.

The current study is a follow-up study of more than 16,000 women enrolled in WHI who were randomized to conjugated equine estrogen 0.65 mg per day plus medroxyprogesterone 2.5 mg per day (Prempro®) or placebo. Participants were followed for an average of 11 years with the main outcome measure being breast cancer incidence and breast cancer mortality. Women on hormone therapy had a higher rate of breast cancer compared to women on placebo (0.42% vs 0.34% per year; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.07-1.46; P = 0.004) and breast cancers in the hormone group were more likely to be node-positive (23.7% vs 16.2%; HR, 1.78; 95% CI, 1.23-2.58; P = 0.03). The death rate associated with breast cancer was higher in the hormone group (0.03% vs 0.01% per year; HR, 1.96; 95% CI, 1.00-4.04; P = 0.049), a finding that barely reached statistical significance because of the low number of cancers in either group.

The authors conclude that estrogen plus progesterone was associated with a higher breast cancer incidence, as well as cancers that were more commonly node-positive. Breast cancer mortality was also higher in the combined hormone group (JAMA 2010;304:1684-1692). An accompanying editorial points out that despite the borderline statistical significance of these findings it is likely that "the increase in breast cancer deaths due to hormone therapy has been underestimated in the current study." However, it is still unclear whether short courses of hormone therapy for relief of postmenopausal symptoms right after menopause may be safe and further research is needed "to determine whether lower doses or shorter durations of hormone therapy could alleviate menopausal symptoms without increasing cancer risk" (JAMA 2010;304:1719-1720).