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A new study suggests that women on estrogen plus progestin are more likely to develop and die from breast cancer.

While most observational studies have linked estrogen plus progestin with more positive outcomes, the latest study published March 29 in the Journal of the National Cancer Institute found that not only is prognosis similar for both users and nonusers of combined hormone therapy, mortality from breast cancer may actually be higher in women who use combined hormone therapy.

After analyzing the Woman's Health Initiative randomized trial and other observational studies, researchers found that postmenopausal women with no prior hysterectomy with negative mammograms and who used estrogen and progestin combined therapy had higher incidence of breast cancer than their nonuser counterparts. They found that women who started hormone therapy closer to menopause had a higher breast cancer risk with a weakening influence as the time from menopause 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," researchers explained in the study.

Catherine Schairer, Ph.D., and Louise A. Brinton, Ph.D., both of the National Cancer Institute, wrote in an accompanying article that questions still remain about whether the latest analysis resolves the differences in tumor prognosis and tumor characteristics found in the observational study and the randomized trial.

"In general, tumors in estrogen plus progestin users in the WHI Observational Study were not significantly different from those in non-hormone 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," Schairer and Brinton wrote.

The recommend additional analyses of currency and duration of hormone use in relationship to tumor development for researchers to establish the tumor characteristics associated with combined hormone therapy.