Chains of evidence, mosaics of data: does estrogen 'cause' breast cancer? How would we know?

There appears to be a broad consensus that estrogen is a cause of breast cancer. Proof of cause and effect in clinical medicine requires a different approach for an epidemiological exposure (a 'mosaic' approach) than for an infectious agent suspected of causing a particular disease (a 'chain of evidence' approach). This paper discusses the differences between these two approaches in determining the relationship between a risk factor and a disease, and assesses the strength of the data linking estrogen with breast cancer. Analysis of existing data, including findings from the Women's Health Initiative, finds that all nine of the criteria necessary for confirming the epidemiological strength of a risk factor are not met in the case of estrogen, raising serious questions about the validity of this widespread assumption.