Postmenopausal hormone therapy increases the risk of breast cancer, but many studies attribute this risk to the combination of estrogen and progestin treatments. In a study by the Women’s Health Initiative, unopposed estrogen was found to have a hazard ratio of 0.77 (adjusted confidence interval, 0.59 to 1.01) for developing breast cancer after seven years of follow-up. Chen and colleagues evaluated whether long-term use of unopposed estrogen increased the risk of invasive breast cancer in postmenopausal women.

The study analyzed data from participants in the Nurses’ Health Study from 1980 to 2002, which included baseline questionnaires with information about cancer and cardiovascular risks and follow-up questionnaires that were mailed every two years. Women who were postmenopausal, had a hysterectomy, and were considered current users of unopposed conjugated estrogens (Premarin) participated in the study. Estrogen use was established through the self-reported information on the questionnaire. As the study progressed, women who became postmenopausal and had a hysterectomy were added to the analysis. The status of estrogen and progesterone receptors for breast cancer was recorded, and the main outcome measure was invasive breast cancer.

At the end of the study, 28,835 women were enrolled. Of the 934 women who had invasive breast cancer, 226 had never used estrogen therapy (see accompanying table). The researchers also found that women who had positive estrogen or progesterone receptors had the highest risk for breast cancer. Additionally, the risk of positive estrogen or progesterone receptor breast cancer was significantly higher in women who had been on unopposed estrogen for more than 15 years.

The authors conclude that long-term use of unopposed estrogen therapy increases the risk of breast cancer, but using estrogen for less than 10 years is not associated with an increased risk. They also note that using estrogen to prevent or treat osteoporosis usually requires long-term therapy; therefore, other options should be considered.