Hormone therapy likely to increase deaths from breast cancer

Issue: November 10, 2010

Longer follow-up data from the Women’s Health Initiative trial show that postmenopausal women who received hormone therapy with estrogen and progestin are more likely to not only get breast cancer, but also more likely to die of breast cancer.

Previous data from the trial showed that breast cancer incidence was increased in women who received HT; however, breast cancer mortality was not reported. The follow-up data, published in the Journal of the American Medical Association, show that women who received HT were more likely to have node-positive breast cancer and also more likely to die of the disease.

“These data support the finding that the increase in deaths from breast cancer is real,” Rowan T. Chlebowski, MD, PhD, of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and a study investigator, said in a statement. “Together with reports that estrogen plus progestin significantly increased deaths from lung cancer, this new study means that about 5½ years of estrogen plus progestin use significantly increased the two leading causes of cancer mortality in women.”

According to the researchers, many observational studies have associated HT use with an increased risk for breast cancer. In these studies, however, the breast cancers had favorable characteristics, lower stage and longer survival than the breast cancers that developed in women who did not use HT. Although the Women’s Health Initiative (WHI) showed an increase in breast cancers, it also showed that HT interfered with breast cancer detection. This led to breast cancers being more advanced in stage when finally discovered.

“The U.K.’s Million Women Study, though not a randomized study, showed that using hormone therapy at breast cancer diagnosis increased the rate of death from breast cancer,” said Doug Yee, MD, director of the Masonic Cancer Center at the University of Minnesota and a HemOnc Today Editorial Board member. “This study is a confirmation of the earlier study, but both studies were a little surprising, as most people thought if the women were going to get breast cancer, it would be low-grade, indolent disease. We see that is not the case.”

Trial results

WHI was a randomized, placebo-controlled trial that included 16,608 postmenopausal women aged 50 to 79 years with no prior hysterectomy. From November 1993 to July 2002, women were randomly assigned HT or placebo. The women were required to receive yearly mammograms and clinical breast exams.

After a mean of 5.6 years, the intervention phase was stopped when data revealed that the risk for invasive breast cancer was increased in women who were assigned HT. There were 349 cases of breast cancer identified at this time. The post-intervention phase continued through to March 2005, the original trial end date. After a mean follow-up of 7.9 years, the risk persisted with 388 cases of breast cancer identified.

The most current results are after a mean follow-up of 11 years. The number of breast cancer cases identified was 678. There were 385 cases in the HT group vs. 293 cases in the placebo group. In addition, patients who received HT were more likely to present with positive lymph nodes: 81 patients vs. 43 patients in the placebo group.

More women in the HT group died of breast compared with the placebo group: 25 deaths vs. 12 deaths. In addition, there were more deaths from all causes in patients in the HT group who developed breast cancer: 51 deaths vs. 31 deaths in the placebo group.

“With 678 invasive cancers in this latest study from the Women’s Health Initiative, one can see an adverse influence on all breast cancer subgroups, not on just favorable ER-positive cancers,” Chlebowski said in an statement.

Hormone therapy usage

In an accompanying editorial, Peter B. Bach, MD, MAPP, a member of the Health Outcomes Research Group in the department of epidemiology and statistics at Memorial Sloan-Kettering Cancer Center, said the WHI was the first trial to reveal the magnitude of the risk of breast cancer in women receiving HT.

“Given the substantial population of women who seek relief from menopausal symptoms [with hormone therapy] and the large potential burden of disease that could be created if medications given to alleviate symptoms today cause cancer and other deaths tomorrow, it seems that additional randomized trials are needed specifically to determine whether lower doses or shorter durations of hormone therapy could alleviate symptoms without increasing cancer risk,” Bach wrote.

Yee said HT should only be used for specific symptoms. “Before WHI, many asymptomatic women received hormone therapy because their physicians thought they were preventing future problems. Now we’ve learned that they were actually creating a problem. Hormone therapy should not be given to asymptomatic women.” – by Emily Shafer

For more information:

Bach PB. JAMA. 2010;304:1719-1720.

Chlebowski RT. JAMA. 2010;304:1684-1692.