American Journal of Epidemiology Advance Access originally published online on October 15, 2008
American Journal of Epidemiology 2008 168(10):1213; doi:10.1093/aje/kwn316
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LETTERS TO THE EDITOR |
RE: "CONJUGATED EQUINE ESTROGENS AND BREAST CANCER RISK IN THE WOMEN'S HEALTH INITIATIVE CLINICAL TRIAL AND OBSERVATIONAL STUDY"
Department of Public Health and Family Medicine, University of Cape Town Medical School, Observatory 7925, South Africa
(e-mail: samshap{at}mweb.co.za)
In their combined analyses of the Women's Health Initiative (WHI) clinical trial and observational study data, Prentice et al. conclude that their findings "... do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs [conjugated equine estrogens]" (1, p. 1407). However, combination of the data was illegitimate. In the observational study, 100% of the women were aware of their exposure. Particularly since they had originally been invited to participate in a clinical trial (1) but had not, greater anxiety among CEE users and their medical attendants made selective detection of otherwise occult breast cancer inevitable.
By contrast, in the clinical trial, <2% of the women had their treatments unblinded (2). The occasional woman might have guessed that she was on CEEs because of breast swelling or tenderness, but otherwise there was little or no opportunity for detection bias.
Given this striking discrepancy, in the WHI studies the most valid estimates of breast cancer risk in CEE users remain those identified in the trial (2)—although, to be sure, the nonadherence rates of >50% also render those estimates suspect.
The clinical trial findings for CEEs also cast doubt on the WHI findings for estrogen plus progestin (3): In that trial, the respective unblinding rates among CEE and placebo recipients were 44% and 7%. That difference was mainly due to persistent vaginal bleeding, and it would have created greater concern about endometrial cancer and, consequently, breast cancer as well among recipients of estrogen plus progestin.
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ACKNOWLEDGMENTS |
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Conflict of interest: The author presently consults, and in the past has consulted, with manufacturers of products discussed in this letter.
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References |
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 TOP References |
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- Prentice RL, Chlebowski RT, Stefanick ML, et al. Conjugated equine estrogens and breast cancer risk in the Women's Health Initiative clinical trial and observational study. Am J Epidemiol. (2008) 167(12):1407–1415.
[Abstract/Free Full Text] - Stefanick ML, Anderson GL, Margolis KL, et al. Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA (2006) 295(14):1647–1657.
[Abstract/Free Full Text] - Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA (2002) 288(3):321–333.
[Abstract/Free Full Text]
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  R. L. Prentice, R. T. Chlebowski, J. E. Rossouw, and G. L. Anderson FOUR AUTHORS REPLY Am. J. Epidemiol., November 15, 2008; 168(10): 1213 - 1214. [Full Text] [PDF]
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