Questions About Data Linking Breast Cancer and HRT

From Medscape Medical News > Oncology Zosia Chustecka January 17, 2012 — The link between breast cancer and hormone replacement therapy (HRT) is based on "unreliable evidence," assert the authors of a paper published online January 16 in the Journal of Family Planning and Reproductive Health Care. However, this criticism has been summarily dismissed by experts involved in the HRT studies. The authors note that the claim that HRT with estrogen plus progestogen is now an established cause of breast cancer is based principally on the findings of 3 studies — the collaborative reanalysis, the Women's Health Initiative, and the Million Women Study (MWS). The findings from these studies, which were reported in the early 2000s, led to warnings about the risk for breast cancer from HRT, and resulted in a dramatic fall in the use of these products. However, these studies do not prove causality, say the authors, headed by Samuel Shapiro, MB, visiting professor of epidemiology at the University of Cape Town Medical School in South Africa. They examined each of the studies in a series of articles, the latest of which focuses on the MWS. "HRT may or may not increase the risk of breast cancer," the authors note, and conclude that these studies do not establish causality. The MWS study estimated a larger risk for breast cancer with HRT than either the collaborative reanalysis or the Women's Health Initiative, and it had a huge impact on regulatory authorities and on the public perception of safety, the authors note. It is the largest study of HRT and breast cancer ever conducted, and its name — the Million Women Study — implies an authority beyond criticism or refutation," they add. However, size alone dose not guarantee that the findings are reliable, they add. After examining the validity of the study in some detail, they conclude that the evidence from the MWS is "unreliable." Dr. Shapiro and colleagues report that there were defects in the study design, and find evidence of detection bias and confounding, issues with internal and external consistency, and other problems. However, the principal investigator of the MWS, Dame Valerie Beral, AC, DBE, FRS, MRCP, professor and head of the Cancer Epidemiology Unit at Oxford University, United Kingdom, dismissed the criticisms. "These issues are not new and have been refuted previously," she said in a statement. She describes the paper by Dr. Shapiro and colleagues as a "restatement of views held by many consultants to HRT manufacturers (as these authors are) attempting to dispute evidence about the adverse effects of HRT." The totality of the worldwide evidence is now overwhelming. The authors neglect to mention that "the MWS findings of an increased risk of breast cancer in users of HRT, especially of estrogen–progestogen combinations, have now been replicated in over 20 other studies," she continued. "The totality of the worldwide evidence is now overwhelming" "In line with the findings from these studies, the recent large decrease in HRT use has been followed in many countries by a nationwide decline in the incidence of breast cancer," Dr. Beral said. In the related statement, Sir Richard Peto, FRS, cofounder and codirector of the Clinical Trial Service Unit, Oxford University, said that the MWS "provides strong biologically plausible evidence of causality — i.e., of an increased probability of getting breast cancer among otherwise similar women (and a rapid decrease after they stop)." "HRT is one of the most important causes of breast cancer in the world, and women can easily change their risk by stopping," Dr. Beral and Dr. Peto conclude. Dr. Shapiro and several coauthors report acting as consultants to manufacturers of HRT products. J Fam Plann Reprod Health Care. Published online January 16, 2012. Abstract