Does hormone replacement therapy (HRT) cause breast cancer? An application of causal principles to three studies

Abstract

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.

Does hormone replacement therapy cause breast cancer? Commentary on Shapiroet al.papers, Parts 1–5

“…A series of critiques of these studies (Parts 1–4)5–8 have been published in previous issues of this Journal. The latest paper in this series (Part 5)9 examines the reported decline in the incidence of breast cancer and possible attribution to the fall in HRT usage post WHI and MWS.…”

A randomized, double-blind, placebo-controlled trial of Chinese herbal medicine granules for the treatment of menopausal symptoms by stages

“…[3][4][5][6][7] The validation of HT in menopause is still debatable. 8 Estrogen and progestin combination could increase the risk of coronary heart diseases according to some studies, 3,9 and prolonged use of HT is associated with high occurrences of breast cancer. 3,10 Therefore, scientists are trying to find a safer but equally effective alternative therapy for menopausal symptoms.…”

5. Hormonal Effects on the Postmenopausal Breast

“…Specifi c evaluation of the 12% using combined MHT revealed risk estimates of 1. risk disappeared within 5 years of cessation of treatment. One very large but controversial study, the MWS ( 9 ), is included in the Collins et al review ( 25 ) and is alluded to below ( 41 ). In 2005, Collins et al ( 25 ) published a comprehensive review of the evidence up to that time, which predominantly represented observational data.…”