Hormone therapy reduced risk for breast cancer after hysterectomy

LaCroix AZ. JAMA. 2011;305:1305-1314.

Issue: May 10, 2011

Postmenopausal women who have undergone hysterectomy had a reduced incidence of breast cancer and cardiovascular events after treatment with conjugated equine estrogens, according to results from the Women’s Health Initiative.

However, researchers said estrogen did not have any effect on coronary heart disease, deep vein thrombosis, stroke, hip fracture, colorectal cancer or total mortality.

Researchers set out to examine health outcomes associated with randomization to treatment with conjugated equine estrogens (Premarin, Wyeth) among women with prior hysterectomy after a mean of 10.7 years of follow-up through August 2009. In the analysis, 3,778 women were assigned to daily 0.625 mg hormone therapy, whereas another 3,867 were assigned to placebo.

Participants were postmenopausal women aged 50 to 79 years recruited at 40 US locations from 1993 to 1998.

Rates of invasive breast cancer were similar during the intervention (HR=0.79; 95% CI, 0.61-1.02) and postintervention phases (HR=0.75; 95% CI, 0.51-1.09) of the study. Women in the estrogen group had a statistically significant lower cumulative incidence of breast cancer compared with the placebo group, 0.27% vs. 0.35% (HR=0.77, 95% CI, 0.62-0.95).

Incidence of colorectal cancer did not differ between the two groups.

Although the risk for stroke, deep vein thrombosis and pulmonary embolism were elevated during the intervention phase for women assigned to estrogen, researchers said the increased risk factor disappeared postintervention. For all cardiovascular events, the HR was 2.26% in the estrogen group vs. 2.12% in the placebo group.

Writing in an accompanying editorial, Emily S. Jungheim, MD, MSCI, and Graham A. Colditz, MD, DrPH, said although these results show that adverse event rates are low and largely limited to current use of unopposed estrogen, there does not appear to be a substantial benefit associated with hormone therapy.

“There may still be a role for short-term use of unopposed estrogen for treating some women with menopausal symptoms, but this role may be vanishing as existing and emerging data continue to be better understood in terms of application to patients,” they wrote. “Despite the evidence linking unopposed estrogen [hormone therapy] use to breast cancer, many clinicians and patients make decisions to use hormone therapy. Clinicians must be aware of the implications of these decisions. They must interpret new and existing data, and must understand the value and limitations of the data when making recommendations.”

Douglas Yee, MD

It is better to administer estrogen alone if it is necessary to treat symptoms. Much of the negative effects associated with hormone replacement therapy are due to the combination of estrogen and progesterone. However, the idea that giving estrogen alone has overall health benefits for asymptomatic women isn’t really supported by this study — these results just suggest that estrogen alone isn’t as bad as estrogen plus progesterone. Plus, we know estrogen is good for bone health, but there are many other choices for bone health that have a protective effect for breast cancer, such as tamoxifen or raloxifene. Estrogen also helps with vaginal dryness, but we have topical combinations that are associated with less systemic risk. There are ways other than estrogen to treat a symptom or prevent a disease that do not carry the same risks.

– Douglas Yee, MD
HemOnc Today Editorial Board member

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