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Estrogen-Only Therapy After Hysterectomy and Breast Cancer Risk

Two new studies confirm that, except with prolonged use, estrogen-only therapy is not associated with increased risk for breast cancer after hysterectomy.

Earlier findings from the Women’s Health Initiative indicated that, in contrast to combined estrogen-progestin therapy, 7 years of estrogen therapy does not increase breast cancer risk following hysterectomy (Journal Watch Women's Health Jun 9 2004).

The latest report from the WHI provides additional findings, including data on mammography and tumor characteristics. Baseline breast cancer risk and prevalence of prior hormone therapy use were similar in the two treatment arms. There was a nonsignificant reduction in risk for invasive breast cancer in the estrogen group (hazard ratio, 0.80; 95% confidence interval, 0.62–1.04). Tumors were larger and more likely to be node-positive in the estrogen group. After the first year, the percentage of mammograms requiring follow-up evaluations was higher in the estrogen group; by the time the study was terminated (mean follow-up, 6.8 years), the cumulative percentage requiring follow-up was 36% in the estrogen group vs. 28% in the placebo group (P<0.001). However, in contrast with the earlier findings for combined estrogen–progestin therapy, mammograms with findings suspicious for cancer were not more common in the estrogen group.

In the latest report from the Nurses’ Health Study, investigators assessed data on almost 29,000 U.S. nurses who had undergone hysterectomy and had reported information regarding their use or nonuse of estrogen at study entry. Overall, 934 cases of invasive breast cancer occurred. Among study participants who had used estrogen for 20 years or longer, the risk for breast cancer was modestly increased (multivariate relative risk, 1.42; 95% CI, 1.13–1.77). For shorter durations of use, no significant increase was observed.

Comment: These findings are consistent: Estrogen-only therapy is not associated with an increased risk for breast cancer after hysterectomy except with prolonged use. Other recent high-quality observational studies in the U.S. and Sweden have also shown a lack of such an association (Menopause 2006 Mar/Apr; 13:160). Women who have had hysterectomies and are considering starting or continuing estrogen therapy for treatment of vasomotor or genital atrophy symptoms, or to prevent osteoporotic fractures, can be counseled that — at least for use measured in years rather than decades — estrogen therapy does not appear to increase breast cancer risk.

— Andrew M. Kaunitz, MD

Published in Journal Watch Women's Health June 30, 2006

Citation(s):

Stefanick ML et al. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 2006 Apr 12; 295:1647-57.

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• Medline abstract (Free)

Chen WY et al. Unopposed estrogen therapy and the risk of invasive breast cancer. Arch Intern Med 2006 May 8; 166:1027-32.

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• Medline abstract (Free)