A critique of the methodology of studies of benign breast disease and breast cancer risk.

After almost a century of research the relationship of benign breast disease to breast cancer risk is still controversial. The present investigation assessed this controversy by examining all published cohort studies that examined the risk of breast cancer in subjects with benign breast disease for their compliance with widely accepted standards for the conduct of etiologic research. Most of these studies describe the breast cancer incidence in women who have had breast biopsies. The 16 standards included a description of the population studied, a definition of benign breast disease, an account of follow-up, and a description of the analysis of risk. Of the 36 studies examined, 22 reported finding an increase in breast cancer risk in women with benign breast disease and all met more methodologic standards than the 11 studies reporting no increase in risk (3 studies reported no conclusions). In particular, none of the 11 "negative" studies calculated the number of cancers expected in the population studied, whereas all 22 "positive" studies did so. There is thus considerable statistical support from well-conducted studies for the view that benign breast disease is associated with an increase in breast cancer risk. By contrast, there is no credible support for the contrary view, which is often based on small studies in which no cancers were observed or on studies whose conclusions are not supported by an appropriate analysis of the data they contain.