Hormone therapy associated with increased invasive breast cancer

Hormone therapy not only increases the risk of breast cancer but its potential to spread to the lymph nodes and possibly also women's risk of dying from the disease, according to a new analysis of the Women's Health Initiative.

In the WHI trial, more than 16,000 postmenopausal women were randomized to receive either combined conjugated equine estrogens (0.625 mg/day) and medroxyprogesterone acetate (2.5 mg/day) or placebo. This new analysis was based on follow up data collected for a mean of 11 years. Follow up information was obtained from 83% of the surviving participants of the trial. The results were published in the Oct. 20 Journal of the American Medical Association.

Among participants providing follow up data, use of estrogen plus progestin was associated with a significantly higher risk of invasive breast cancer (385 cases vs. 293 cases; hazard ratio [HR], 1.25; P=0.004). The cancers in the active and placebo groups were similar in histology and grade, but women who took the active pills were more likely to have lymph-node involvement in their cancer (81 cases [23.7%] vs. 43 [16.2%]; HR, 1.78; P=0.03). These findings differ from previous observational studies which have found hormone use to be associated with breast cancers with more favorable characteristics, possibly because observational trials are confounded by the tendency of hormone users to have more mammograms, the study authors said.

The analysis also found that the group taking hormones had more deaths directly attributed to breast cancer (25 deaths vs. 12 deaths; HR, 1.96; 95% confidence interval [CI], 1.00-4.04; P=0.049) and more deaths from all causes after breast cancer diagnosis (51 deaths vs. 31 deaths, HR, 1.57; CI, 1.01-2.48; P=0.045). The actual mortality rate from breast cancer likely lies somewhere between these two statistics, the study authors noted, but the all-cause deaths may also reflect the problematic effect of hormones on lung cancer growth and spread.

The confidence intervals and P values for the mortality risks indicate that the difference between groups was not very significant, an accompanying editorial said. However, the direction of the statistical curves suggests that longer follow up could reveal that the damaging effects of hormone therapy have actually been underestimated, the editorialist speculated. He urged caution in the use of hormone therapy, even when using briefer courses of the drugs than the WHI included.

Currently, a safe interval for combined hormone therapy use cannot be reliably defined, the study authors also concluded. Given the scientific uncertainty, patients cannot be informed enough about the risks and benefits to make a valid decision, the editorialist said. He called for additional randomized trials of lower doses and shorter durations of hormone therapy.