The authors of the 2003 Million Women Study were wrong to conclude their investigation proved that hormone replacement therapy (HRT) caused cancer, according to a series of articles published this week in the Journal of Family Planning and Reproductive Health. The study, long used to establish causal links between HRT and breast cancer is severely flawed, a group of epidemiologists have charged.
The observational Million Women Study (MWS), conducted in the U.K., doesn’t adequately satisfy several criteria for causality — including information bias, detection bias, and biological plausibility — and thus can’t be used to conclude that HRT causes breast cancer, according to Samuel Shapiro, PhD, of the University of Cape Town in South Africa, and colleagues.
The study of one million women who presented for routine mammograms in the United Kingdom asked participants to complete a questionnaire about hormone therapy and the risk of breast cancer. The researchers looked at the rate at which breast cancer was diagnosed in these women and their history of using hormone replacement therapy.
The study included women in the U.K. ages 50 to 64 who were eligible for mammography every three years from 1966 to 2001, and who were subsequently followed via questionnaire. Analyses were released in 2003, 2004, 2006, and 2011, and found significantly increased risks of breast cancer with use of estrogen plus progestogen HRT.
The authors claimed the study definitively proved hormone therapy caused breast cancer.
“HRT may or may not increase the risk of breast cancer, but the MWS did not establish that it does,” they wrote in the Journal.
Several experts not involved in the study, however, have emphasized that they’re well aware of the limitations of observational studies such as the MWS, and that the totality of evidence thus far has shown a strong association between HRT and breast cancer.
“This report would not change how I counsel women, as multiple studies, including a randomized trial, have shown an increased risk of breast cancer from combination hormone therapy,” Kathy Helzlsouer, MD, director of the prevention and research center at Mercy Medical Center in Baltimore, said in an email to MedPage Today and ABC News.
The analysis of the Million Women Study is the latest in a series of four papers by the Shapiro group exploring the credibility of three studies — the MWS, the Women’s Health Initiative (WHI), and the collaborative reanalysis (CR) — that causally linking HRT, particularly estrogen plus progestogen therapy, with breast cancer.
The earlier papers similarly found that neither the CR nor the WHI could satisfy criteria for establishing causality.
In the latest analysis, Shapiro and colleagues evaluated whether the evidence in the MWS was consistent with generally accepted principles of causality: time order, information bias, detection bias, confounding, statistical stability, duration-response, internal consistency, external consistency, and biological plausibility.
Shapiro and colleagues found the study was lacking across nearly all of the categories establishing causality.
“The name ‘Million Women Study’ implies an authority beyond criticism or refutation,” they wrote. “Yet … size alone does not guarantee that the findings are reliable.”
“If the evidence was unreliable, the only effect of its massive size would have been to confer spurious statistical authority to doubtful findings,” they wrote.