The so-called Million Women Study (MWS) unleashed headlines when it was first published in 2003.
Based on questionnaires returned by more than a million post-menopausal women in Britain, it said hormone replacement therapy (HRT) led to a rise in breast-cancer incidence.
Its estimate caused a wave of anxiety — and much confusion — among regulators and doctors and among women using HRT.
HRT uses the female hormones oestrogen or progestogen, sometimes combined, to ease menopausal symptoms such as hot flushes, loss of sex drive and vaginal dryness.
Updates of the MWS have finetuned the perceived risk. The MWS website says there’s an increased cancer risk of 30 percent in oestrogen-only treatment, and a twofold risk in oestrogen-progestogen therapy, compared with women who do not take these drugs.
The risk increases the longer a woman uses HRT, but drops to normal level within five years after stopping use, the MWS says.
But an assessment published on Monday in the Journal of Family Planning and Reproductive Health says the MWS’s design has so many problems that a safe conclusion cannot be drawn.
“HRT may or may not increase the risk of breast cancer, but the MWS did not establish that it does,” the paper says bluntly.
Among half a dozen points, the authors say cancers detected within a few months of the study’s start would have already been present when the women were enrolled.
The review also points to “detection bias” through the choice of participants.
The volunteers were taking part in a breast screening programme when they were invited to join the study.
They would thus have already known about breast lumps and suspect lesions that point to breast cancer. As a result, the MWS found a 40-percent higher incidence of breast cancer among its volunteers — regardless of whether they used hormone therapy or not — than in the population at large.
“The name ‘Million Women Study’ implies an authority beyond criticism or refutation,” say the authors, led by Samuel Shapiro, a professor of public health at the University of Cape Town, South Africa.
“Yet the validity of any study is dependent on the quality of its design, execution, analysis and interpretation. Size alone does not guarantee that the findings are reliable.”
In an email to AFP, the leaders of the MWS rebutted the criticism, saying that more than 20 studies had replicated its findings and a decline in the use of HRT had led to a fall in cases of breast cancer.