Study: Combined HT linked to breast cancer risk

Estrogen plus progestin use is linked with increased breast cancer incidence, according to a study.

Researchers also found that prognosis is similar for users and nonusers of combined hormone therapy, suggesting that mortality from breast cancer may be higher for hormone therapy users.

In a Women’s Health Initiative randomized trial, estrogen plus progestin was associated with an increase in both breast cancer incidence and mortality. However, most observational studies have linked estrogen plus progestin with better outcomes.

To determine the differences between the WHI trial and other observational studies, Rowan T. Chlebowski, MD, PhD, of the Los Angeles Biomedical Research Institute, and colleagues, conducted an observational study of more than 41,000 postmenopausal women with no prior hysterectomy and with negative mammograms within the past two years.

The researchers found that breast cancer incidence was notably higher in estrogen plus progestin users than incidence in nonusers over an 11-year period. Women who started hormone therapy closer to menopause had a higher breast cancer risk, with a weakening influence as the time separation increased.

“Because survival after breast cancer diagnosis did not differ between estrogen plus progestin users and nonusers, the higher breast cancer incidence of those using estrogen plus progestin may lead to increased breast cancer mortality on a population basis,” according to the study, which was published March 29 on the website of the Journal of the National Cancer Institute.

In a news release, Chlebowski commented that the study “shows that women who begin the hormonal therapy of estrogen plus progestin closer to menopause are at a greater risk of breast cancer. … Because menopause usually is the reason for women to undergo hormonal therapy, this is a very significant finding.

“The study also showed that all categories of breast cancer are increased — not just those with favorable prognosis — among women using estrogen plus progestin. This finding suggests higher mortality from breast cancer among women who use this combined hormone therapy. As always, women should consult with their physicians and consider the potential risks of any hormonal therapy to help relieve the symptoms of menopause.”

In an accompanying editorial, Catherine Schairer, PhD, and Louise A. Brinton, PhD, both of the National Cancer Institute, wrote that questions remain about whether the data analyzed from the WHI observational study resolves the differences in tumor prognosis and tumor characteristics when compared with the WHI randomized trial.

“In general, tumors in estrogen plus progestin users in the WHI observational study were not significantly different from those in nonhormone users with regard to number of positive lymph nodes or tumor size, but were more likely to be well-differentiated and positive for hormone receptors, findings which are similar to other observational studies,” they wrote.

These findings did not translate into a survival benefit, however. The writers recommended further analyses in this and other data-sets of currency and duration of hormone use in relationship to tumor development to fully resolve the issue of tumor characteristics associated with estrogen plus progestin therapy.

The study abstract is available at

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