Does hormone replacement therapy (HRT) cause breast cancer? An application of causal principles to three studies
- Samuel Shapiro1,
- Richard D T Farmer2,
- John C Stevenson3,
- Henry G Burger4,
- Alfred O Mueck5,
- Anne Gompel6
- 1Visiting Professor of Epidemiology, Department of Epidemiology, University of Cape Town, Cape Town, South Africa
- 2Emeritus Professor of Epidemiology, Department of Epidemiology, University of Surrey, Guildford, UK
- 3Consultant Physician and Reader in Metabolic Medicine, National Heart and Lung Institute, Imperial College, London and Brompton Hospital, London, UK
- 4Emeritus Director, Prince Henry's Institute of Medical Research, Monash Medical Centre, Clayton and Consultant Endocrinologist, Jean Hailes Medical Centre for Women, Clayton, Victoria, Australia
- 5Professor of Clinical Pharmacology and Endocrinology, Department of Endocrinology, University Women's Hospital, Tubingen, Germany
- 6Professor of Gynaecology, Gynaecological Endocrinology Unit, Paris Descartes University, APHP, Port-Royal Hospital, Paris, France
- Correspondence to Professor Samuel Shapiro, Department of Public Health and Family Medicine, University of Cape Town Medical School, Anzio Road, Observatory, Cape Town, South Africa;
- Received 9 October 2012
- Accepted 8 November 2012
Background Based principally on findings in three studies, the Collaborative Reanalysis (CR), the Women's Health Initiative (WHI), and the Million Women Study, it is claimed that hormone replacement therapy (HRT) is an established cause of breast cancer. The authors have previously reviewed those studies (Parts 1–4). The WHI findings were first published in 2002, following which the use of HRT rapidly declined. A correspondingly rapid decline in the incidence of breast cancer has been reported, and attributed to the drop in the use of HRT. The evidence, however, is conflicting.
Methods Using generally accepted causal criteria, in this article (Part 5) the authors evaluate reported trends in the incidence of breast cancer.
Results The evidence to suggest a correlated decline in the incidence of breast cancer following a decline in the use of HRT has not adequately satisfied the criteria of time order, detection bias, confounding, statistical stability and strength of association, internal consistency, and external consistency; biological plausibility is difficult to assess.
Conclusions Based on the observed trends in the incidence of breast cancer following the decline in HRT use, the ecological evidence is too limited either to support or refute the possibility that HRT causes breast cancer.