Conjugated equine estrogen increases benign breast disease risk

Women who took conjugated equine estrogen, a commonly prescribed form of estrogen, had more than twice the risk of developing specific types of benign breast disease as women who took a placebo, according to a randomized controlled trial published online April 8 in the Journal of the National Cancer Institute.

The impact of conjugated equine estrogen on the risk of developing benign proliferative breast disease, a condition that is associated with increased risk of breast cancer, has been unclear. Some studies have reported an association while others have not. In the Women's Health Initiative study, 10,739 postmenopausal women with hysterectomy were assigned to either conjugated equine estrogen or a placebo. Previous analyses did not show an increase in breast cancer incidence in the women who took estrogen alone after a median follow-up of seven years.

To determine whether the hormone increases the risk of benign proliferative breast disease, Tom Rohan, M.D., Ph.D., of the Albert Einstein College of Medicine in New York and colleagues identified and examined non-cancerous breast biopsies in each of the Women's Health Initiative trial arms.

A total of 232 cases of benign proliferative breast disease were identified, with 155 cases among the women who took estrogen supplements and 77 in the placebo group. The risk of developing benign disease increased by more than two-fold for women taking conjugated equine estrogen, compared with those taking a placebo.

“The prevailing hypothesis concerning the natural history of breast cancer is that benign proliferative breast disease without atypia, proliferative disease with atypia, and in situ cancer represent successive steps preceding the development of invasive breast [cancer]. In keeping with this hypothesis, women with benign proliferative breast disease have an increased risk of subsequent breast cancer,” the authors write.

Although the women taking conjugated equine estrogen have not yet shown a significant increased risk of breast cancer in the Women's Health Initiative study, if this hypothesis holds true, they might show increased risk later. Ongoing follow up of the study participants may help to resolve this issue.

http://jncicancerspectrum.oupjournals.org/