Hormone-replacement therapy and the risk of breast cancer

At least 30 epidemiologic studies designed to identify an association between hormone-replacement therapy and breast cancer risk have been published since 1974. In general, the design, quality, and analytic strategies used in these studies have improved over the years, and the number of subjects in each study has increased. The results from studies published prior to 1985 can be summarized as showing a small increase in the risk of breast cancer after many years of estrogen use. Even this tentative conclusion is debatable, however, since many rigorous studies showed no association between estrogen use and breast cancer. This review will summarize the earlier findings and emphasize several large, recent studies that add at least two new dimensions to this body of research; they provide data from Europe and on the addition of progestins to the therapeutic regimen. This review indicates the following: 1. Analyses of ever versus never use of estrogen-replacement therapy show no association with breast cancer risk. 2. Duration of estrogen-replacement therapy affects risk. Based on studies in the United States, a relative risk of about 1.5 may be reached after 15 or more years of use. 3. The increase in risk after long-duration hormone use is present for women with either a natural or a surgical menopause. 4. European studies exhibit higher risks after shorter durations of hormone use than do US studies. 5. The type of estrogen used and the addition of progestins to hormone-replacement therapy may alter the risk of breast cancer. Data that substantiate these points are reviewed and placed in context with hormonal theories of carcinogenesis.