Oral contraceptives and breast cancer. A meta-analysis

Abstract

Since the relationship between oral contraceptive use and breast cancer has not been consistent we undertook a meta-analysis of studies published to date. Papers were located by searching the MEDLINE data base, supplemented by a hand search of all the references in the articles recovered. Studies were graded as to quality. Those judged as probably unbiased were included in the analysis. The method of Woolf was used to combine relative risks. Forty-seven studies were collected: 40 case-control and 7 cohort studies. Thirty-nine of these were considered unbiased. The main results observed were: RR was 1.06 (1.02-1.10) for all studies and 1.14 for premenopausal cancer. For premenopausal cancer, higher RRs were observed in women who early used oral contraceptives with a significant linear dose-response effect: 1.25 (1.10-1.44) in OC users before age 25, and 1.17 (1.06-1.30) in users before the first full-term pregnancy. We conclude oral contraceptive use may be a risk factor for premenopausal breast cancer. Limitations to our research are discussed.

PIP: 40 case control and 7 cohort studies of the link between oral contraceptives and breast cancer were combined in a meta-analysis by the method of Woolf to estimate overall relative risks. Articles were found by a Medline search from January 1966-June 1990, a hand search of the references, and a journal search for 1990. Papers were graded for bias by 2 blinded readers. The analysis of the 39 studies considered unbiased generated a global relative risk of 1.06, and an increased risk of 1.06, and an increased risk of 1.14 for premenopausal breast cancer. For premenopausal cancer, risks were 1.25 for use before age 24, and 1.17 for use before the 1st term pregnancy. A significant linear dose response was seen, in terms of months of exposure. There was an indication of latency, since risk estimates were higher from data collected after 1981. There was no evidence of a relationship between pill use and parity, family history, or history of benign breast disease. The dad are consistent with the theory that oral contraceptives can be acting as cancer initiators or promoters. There was not enough data to judge whether users of current lower dose pills have lower risks for premenopausal breast cancer. Future studies should address the difference between premenopausal and postmenopausal cancer.