Do oral contraceptive agents affect the risk of breast cancer? A meta-analysis of the case-control reports.

BACKGROUND We designed a study to assess the association of oral contraceptive use and the development of breast cancer for women in the following groups: (1) ever oral contraceptive users, (2) long-term oral contraceptive users, and (3) oral contraceptive users before a first full-term pregnancy. METHODS A MEDLINE search of studies published in English from 1966 to 1990 was conducted using the following key words: "oral contraceptive and breast carcinoma." Eligible studies included all published case-control reports of nonduplicated data on a population (hospital or community-based). The following data were extracted from each report: country, age of subjects, number of cases and controls, whether it was a hospital or community-based study, and results. Two evaluators using a quality-assessment instrument independently and blindly reviewed the methods and data analysis section from each eligible study. In the category of "ever oral contraceptive users," an estimate of the pooled relative risk with 95 percent confidence intervals (CIs) was calculated. In the categories of "duration of oral contraceptive use" and "duration of oral contraceptive use before a first full-term pregnancy," Spearman's rank correlation coefficient (rs) was calculated. RESULTS For the categories of "ever oral contraceptive users" and "long-term oral contraceptive users," no association between the use of oral contraceptives and the development of breast cancer could be detected (pooled relative risk "ever oral contraceptive users" = 1.07, 95 percent CI 0.78 to 1.36, rs "duration of use" -0.153, P = 0.189). For the category of "oral contraceptive use before a first full-term pregnancy," a significant correlation was found (rs = +0.497, P = 0.011). Many reports failed to demonstrate adequate protection against the biases most relevant to case-control methods (namely, recall bias, interviewer bias, surveillance bias, and nonresponse bias) and therefore received low-quality scores. CONCLUSIONS This meta-analysis suggests a possible increased risk for breast cancer in women who use oral contraceptives before a first full-term pregnancy. The data, however, are confounded by studies that are generally of low quality. Further studies addressing the risk for breast cancer in oral contraceptive users need to be designed with methods that limit the biases inherent in case-control studies.