The postmenopausal estrogen/breast cancer controversy
J. B. Henrich
Department of Medicine, Yale University School of Medicine, New Haven, Conn.
OBJECTIVE--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. DATA SOURCE AND
SELECTION--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. DATA
EXTRACTION--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. DATA SYNTHESIS--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. CONCLUSION--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.
