The relation between the risk of breast cancer before 45 years of age and oral contraceptive use was examined in a case-control study conducted in New York, Philadelphia, Baltimore, and Boston from 1983 to 1986 of 407 patients with breast cancer and 424 controls. With allowance for confounding, for ever use, the multivariate relative risk estimate was 2.0 (95% confidence interval (CI), 1.4-2.9). For less than 10 years of use, the estimate approximated 2.0 in all categories of duration, including less than three months; for 10 or more years of use it was 4.1 (95% CI, 1.8-9.3). The association was apparent in virtually all subgroups examined, including younger and older women, and women at low and high underlying risk of breast cancer. Contrary to some previous reports, the association was not stronger for use before a first term pregnancy or at an early age. The results suggest that oral contraceptive users, particularly those with very long durations of use, may be at increased risk of breast cancer. However, information bias, particularly for short-term use, could not be ruled out. There may also have been selection bias if oral contraceptive users were under more intensive medical surveillance. It has not been possible to reconcile the findings of the various studies to date, including the authors' earlier results showing no association. The latter results were derived from data collected using methods almost identical to those used in the present study.
PIP: Previous studies have indicated that longterm use of oral contraceptives does not increase the risk of breast cancer. This study of 407 women aged 25-44 with breast cancer and 424 controls indicates otherwise. Ever use among patients was 72% and among controls 59%. For each 5-year age group breast cancer risk was calculated by multivariate analysis and by logistic regression after adjusting for age, geographic area (New York City, Philadelphia, Baltimore, and Boston), interview year, age at 1st term pregnancy, parity, age at menarche, menopausal status, family history of breast disease, body mass, alcohol drinking, education, religion, and health history. The relative risk estimates for 5-9 years of oral contraceptive use was 2.0. For 10 or more years of use, it was 4.1. Overall, for 5 or more years of use, the multivariate relative risk estimate was 2.4. For women aged 25-34 and 35-44, the multivariate risk estimates for 5 or more years of use were 3.3 and 2.4 respectively. Risk estimates rose for nulliparas, for women exposed before 1st term pregnancy, and for parous women exposed only after 1st term pregnancy. For women with low overall baseline risk, the multivariate relative risk estimate was 1.8. For use lasting at least 5 years, the risk among women with low baseline risk was 4.7. Use before 1st pregnancy or at an early age did not increase risk estimates. This study indicates that the risk of breast cancer is increased among women under 45 who have ever used oral contraceptives. For use of less than 10 years, the risk is doubled, and for use of over 10 years, it is quadrupled. The discordant findings of this and previous studies may be due to recall or selection bias, to insufficient numbers of women with the various risk factors or in specific age groups, or to varying formulations of the different oral contraceptive agents.