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Estrogen reduced breast cancer risk in WHI follow-up cohort
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Postmenopausal women with hysterectomy who used estrogen for a median of 5.9 years as part of a Women’s Health Initiative randomized trial experienced a significant reduction in invasive breast cancer incidence, despite published data on the contrary.
According to researchers, the reduced incidence continued for the follow-up period — a median of 4.7 years — after therapy discontinuation.
The randomized, double masked, placebo-controlled WHI trial included 10,739 postmenopausal women aged 50 to 79 years who underwent hysterectomy and were enrolled between 1993 and 1998. Women were randomly assigned to oral conjugated equine estrogen at 0.625 mg/day (n=5,310) or placebo (n=5,429).
Due to an adverse effect of treatment on stroke incidence, the intervention was stopped early on Feb. 29, 2004.
However, follow-up continued until March 31, 2005, at which time 9,786 participants were still living. Researchers obtained consent for extended surveillance (to Aug. 14, 2009) among 7,645 of the living participants and examined the long-term effects of estrogen on invasive breast cancer incidence, tumor characteristics and mortality during this time.
Compared with placebo, estrogen use for a median of 5.9 years was associated with a lower incidence of invasive breast cancer after a median follow-up of 11.8 years (HR=0.77; 95% CI, 0.62-0.95). According to the researchers, there was no difference between the intervention and post-intervention phase effects (HR=0.79; 95% CI, 0.61-1.02 and HR=0.75; 95% CI=0.51-1.09).
However, according to researchers, women at an increased risk for breast cancer may not experience the same benefits as those without a higher risk. The reduction associated with estrogen was concentrated in women without benign breast disease (P=.01) and those without a family history of breast cancer (P=.02).
Breast cancer-related mortality was lower in the estrogen group compared with controls (six deaths, 0.009% per year vs. 16 deaths, 0.024% per year; HR=0.37; 95% CI, 0.13-0.91). Additionally, fewer women died of any cause after a breast cancer diagnosis in the estrogen group vs. the controls (30 deaths, 0.046% per year vs. 50 deaths, 0.076%; HR=0.062; 95% CI, 0.39-0.97).
Despite their results, the researchers said the use of estrogen for the purpose of breast cancer risk reduction is not supported by these findings.
“Although a reduced risk of breast cancer incidence and mortality was noted in recipients of estrogen, these findings do not support its use for breast cancer risk reduction in light of the lack of benefit for populations at higher risk, the adverse effects on stroke and venous thromboembolism and the increased risk reduction available with other drugs,” they wrote.
In an accompanying editorial, Anthony Howell, MD, and Jack Cuzick, PhD, said these results should be viewed in the context of a 2011 update study detailing the effects of estrogen on overall health that was published in The Journal of the American Medical Association. According to those results, there was no overall difference in global health index. However, the null result masked an important interaction with age, demonstrating health improvements in young women and health decrements in older women.
“The WHI investigators should be congratulated for providing insight into the value of conjugated equine estrogens and young women can be reassured of the low risks and potentially striking benefits, provided that they are consulted about the small increases in thromboembolic disease as noted with most hormonal preparations,” wrote Howell, of the Genesis Prevention Center at the University Hospital of South Manchester in the United Kingdom, and Cuzick, of the Center for Cancer Prevention at Queen Mary University of London and the Wolfson Institute for Preventive Medicine in the United Kingdom.
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Disclosure: Rowan T. Chlebowski, MD, has been a consultant for Amgen, AstraZeneca, Novartis and Pfizer; has received funding support from Amgen and served on speakers’ bureaus for AstraZeneca and Novartis. The other researchers report no relevant financial disclosures.