Based principally on three studies’ findings, the collaborative reanalysis, the WHI, and the Million Women Study, it is claimed that HRT with estrogen plus progestogen is now an established cause of breast cancer. The authors have previously reviewed the findings in the CR and WHI.

Researchers conducted this study to evaluate the evidence for causality in the MWS.

The authors evaluate the findings using generally accepted causal criteria in the MWS for E+P and ET in this article.

Despite the massive size of the MWS, the E+P and ET findings did not adequately satisfy the criteria of time order, information bias, detection bias, confounding, statistical stability and strength of association, duration-response, and internal consistency, external consistency, or biological plausibility. Had detection bias resulted in the identification in women aged 50–55 years of 0.3 additional cases of breast cancer in ET users per 1000 per year, or 1.2 in E+P users, it would have nullified the apparent risks reported.

The study concluded that HRT may or may not increase breast cancer risk, but the MWS did not establish that it does.