The postmenopausal estrogen/breast cancer controversy

To provide an overview of the postmenopausal estrogen/breast cancer controversy emphasizing the sources of disagreement in the literature and their clinical and research implications.

A MEDLINE search of the English-language literature and a review of bibliographies of meta-analyses describing the association between postmenopausal estrogen use and breast cancer risk.

Twenty-four original articles and three meta-analyses were reviewed. In addition, five studies that attempted to minimize detection bias were reviewed to assess the potential role of this bias on risk estimates.

Among the original articles, risk estimates ranged from a protective to an adverse effect in women who ever used estrogens; no consistent quantitative effects of estrogens on breast cancer risk were found. In the meta-analyses, summary risk estimates were not significantly elevated in women who ever used estrogen. Findings from European-based studies may account for the increased risk associated with increasing duration of use reported in one meta-analysis. In studies that controlled for detection bias, risk estimates were 1 or less in the ever-used category; there was no consistent effect across other categories of use.

These findings do not support an overall increased risk of breast cancer in women who ever used postmenopausal estrogens or a conclusive or consistent effect across other measures of use. Cross-national differences in estrogen use and inequalities in breast cancer detection between estrogen users and nonusers may account for the increased risk estimates reported in some studies. Newer estrogen and progestin-opposed regimens need to be evaluated further.