Hormone‐replacement therapy and the risk of breast cancer

At least 30 epidemiologic studies designed to identify an associationbetween hormone‐replacement therapy and breast cancer risk have beenpublished since 1974. In general, the design, quality, and analyticstrategies used in these studies have improved over the years, and thenumber of subjects in each study has increased. The results from studiespublished prior to 1985 can be summarized as showing a small increase inthe risk of breast cancer after many years of estrogen use. Even thistentative conclusion is debatable, however, since many rigorous studiesshowed no association between estrogen use and breast cancer. This reviewwill summarize the earlier findings and emphasize several large, recentstudies that add at least two new dimensions to this body of research; theyprovide data from Europe and on the addition of progestins to thetherapeutic regimen. This review indicates the following: 1. Analyses ofever versus never use of estrogen‐replacement therapy show no associationwith breast cancer risk. 2. Duration of estrogen‐replacement therapyaffects risk. Based on studies in the United States, a relative risk ofabout 1.5 may be reached after 15 or more years of use. 3. The increase inrisk after long‐duration hormone use is present for women with either anatural or a surgical menopause. 4. European studies exhibit higher risksafter shorter durations of hormone use than do US studies. 5. The type ofestrogen used and the addition of progestins to hormone‐replacement therapymay alter the risk of breast cancer. Data that substantiate these pointsare reviewed and placed in context with hormonal theories ofcarcinogenesis.