The Million Women Study, a U.K. project that found hormone replacement therapy led to increased risk of breast cancer, had flaws that call into question the findings, according to a review of the evidence led by a South African researcher.
Design flaws, such as including cases of cancer detected within a few months of the start of the study and using participants involved in a breast screening program, may have skewed the findings, according to the analysis led by Samuel Shapiro at the University of Cape Town Medical School.
The Million Women Study, begun in 1996 and conducted by Cancer Research U.K. and the National Health Service, involves more than a million participants in the U.K. age 50 and over. Users of estrogen-progestogen hormone replacement therapy, or HRT, had twice the risk of developing breast cancer compared with non-users, and HRT use by women aged 50 to 64 between 1993 and 2003 resulted in about 20,000 additional cases of breast cancer, according to the study.
“We conclude that the evidence in the MWS was indeed unreliable,” Shapiro and his authors wrote in an article published today in the Journal of Family Planning and Reproductive Health Care. “HRT may or may not increase the risk of breast cancer, but the MWS did not establish that it does.”
Hormone therapy is prescribed to women to ease the symptoms of menopause. Reduced estrogen levels during menopause may cause the part of the brain responsible for temperature control to malfunction, according to the North American Menopause Society, a nonprofit organization based in Mayfield Heights, Ohio. Hot flashes strike suddenly and can be accompanied by rapid heartbeat, nausea, dizziness, headaches, muscle weakness and fatigue.
For the most aggressive forms of cancer, it is generally accepted that it takes a decade for a tumor to reach the size of 1 centimeter, which is the smallest size that can be diagnosed clinically, according to the authors. Therefore, it is “implausible” that HRT use, which was less than seven years in the study, could have increased the risk of breast cancer, they said.
“The authors omit to say that Million Women Study findings, of an increased risk of breast cancer in users of HRT, especially of estrogen-progestogen combinations, have been replicated in over 20 other studies,” said Valerie Beral, a lead researcher for the Million Women Study and director of the cancer epidemiology unit at Oxford University in Oxford, England, in an e-mailed statement. “The totality of the worldwide evidence is now overwhelming.”
Shapiro and three of his co-authors are consultants for manufacturers of HRT products, according to their disclosure in the article. The other co-author has been a consultant in the past. Wyeth, acquired in October 2009 by New York-based Pfizer Inc. for $68 billion, is the largest maker of hormone replacement drugs.
“This paper is a re-statement of views held by many consultants to HRT manufacturers -- as these authors are -- attempting to dispute evidence about the adverse effects of HRT,” Beral said.
The recent large decrease in HRT use has been followed in many countries by a nationwide decline in the incidence of breast cancer, Beral said.