Estrogen replacement therapy and the risk of breast cancer: results from the case-control surveillance study

To examine the relation of noncontraceptive estrogen use to the risk of breast cancer among postmenopausal women, the authors conducted a case-control study: 1,686 cases were compared with 2,077 hospital control subjects, of whom 1,120 had non-gynecologic cancers and 957 had nonmalignant (also non-gynecologic) conditions. Data were obtained from 1980 to 1986, by interview of subjects in hospitals in the United States and Canada. The relative risk estimate for any use of replacement estrogens unopposed by progestogens was 1.2 (95% confidence interval (Cl) 1.0-1.4), after adjustment for age and type of menopause; when all known risk factors for breast cancer were taken into account in a multivariate analysis, the estimate was similar. For use of at least 15 years duration, the estimate was 0.9 (95% Cl 0.5-1.9). Most of the unopposed use was of conjugated estrogens: overall, the relative risk (95% Cl) was 1.3 (1.0-1.6); for durations of 15 or more years, it was 0.9 (0.4-1.9); for use of 5 years followed by a latent interval of 15 or more years, it was 1.3 (0.7-2.4); and for current use it was 1.1 (0.7-1.6). There was no evidence of increased breast cancer risk when the conjugated estrogen users were divided according to dose. There was little use of estrogens opposed by progestogens; the relative risk estimate was 1.7 (95% Cl 0.9-3.3). The results of this large study provide no evidence that the use of unopposed conjugated estrogens increases the risk of breast cancer, even after long durations of use or long latent intervals, but the possibility of a modest increase (less than a doubling) could not be excluded. There were insufficient data to evaluate the effects of nonconjugated estrogens and of combined estrogen and progestogen therapy.