Women who used estrogen-only hormone replacement therapy (HRT) to ease postmenopausal symptoms following hysterectomy appear to be nearly 25% less likely to develop breast cancer and nearly 63% less likely to die from the disease once it is diagnosed compared with women who did not use estrogen, indicate the results of a recent analysis presented in The Lancet Oncology. However, these findings do not support the use of estrogen to reduce breast cancer risk in women at heightened risk for the disease.

A team led by Garnet L. Anderson, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, evaluated extended follow-up data from postmenopausal women enrolled in the Women’s Health Initiative between 1993 and 1998. These 10,739 women, aged 50 to 79 years at enrollment, had undergone hysterectomy and had been randomized to receive oral conjugated equine estrogen (0.625 mg/day) or placebo. Although estrogen therapy ended in February 2004 due to an adverse effect on stroke risk, follow-up continued until the trial’s planned termination date of March 31, 2005, and 7,645 participants then agreed to extended surveillance. This allowed Anderson’s team to review data collected as of mid-August 2009—a median 4.7 years after estrogen therapy was discontinued.

The researchers determined that after a median follow-up of 11.8 years, the use of estrogen for a median of 5.9 years was associated with a 23% lower incidence of invasive breast cancer compared with placebo (151 cases, 0.27% per year vs 199 cases, 0.35% per year). No difference was seen between intervention phase and postintervention phase effects.

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Estrogen users who did develop breast cancer were 63% less likely to die from the disease (six deaths, 0.009% per year) than were placebo users (16 deaths, 0.024% per year). In addition, fewer estrogen users died from any cause after a breast cancer diagnosis (30 deaths, 0.046% per year) than did controls (50 deaths, 0.076% per year).

Subgroup analyses demonstrated that breast cancer risk reduction with estrogen use was concentrated in women who did not have benign breast disease or a family history of breast cancer, leading the researchers to caution against using estrogen to reduce breast cancer risk in women falling into these high-risk categories who are also at increased risk for stroke or blood clots.