Oral contraceptive and breast cancer

Vol. 11, 1375–1381, November 2002

Cancer Epidemiology, Biomarkers & Prevention

1375

Use of Oral Contraceptives and Breast Cancer Risk: The NorwegianSwedish Women’s Lifestyle and Health Cohort Study1

Merethe Kumle,2 Elisabete Weiderpass, Tonje Braaten, Ingemar Persson, Hans-Olov Adami, and Eiliv Lund
Institute of Community Medicine, University of Tromsoe, 9037 Tromsoe, Norway [M. K.,T. B., E. L.]; Department of Medical Epidemiology, Karolinska Institutet, S-17177 Stockholm, Sweden [E. W., H-O. A.]; IARC, F-69372 Lyon, France [E. W.]; and Medical Products Agency, S-75103 Uppsala, Sweden [I. P.]

Abstract Current use of oral contraceptives (OCs) has been reported to increase breast cancer risk slightly. In 1991/ 1992, a prospective cohort study specifically designed toexamine the role of hormonal contraceptives in relation to breast cancer was conducted in Norway and Sweden. This study was entitled Women’s Lifestyle and Health. Of 196,000 invited women aged 30 – 49 years, 106,844 women answered a 4-page questionnaire. Altogether, 103,027 women providing information on contraceptive use were included in the analysis presented here, and 1,008 primary invasive breastcancers were diagnosed throughout 1999 (end of follow-up). Proportional hazard regression was used to calculate relative risks (RRs) with adjustment for age and other possible confounders. An increased breast cancer risk was observed among women who were current/recent users of OCs of any type at the start of follow-up [RR, 1.6; 96% confidence interval (CI), 1.2–2.1]. Current/recent use (i.e., usein the year preceding cohort enrolment) of combined OCs (RR, 1.5; 95% CI, 1.0 –2.0) and progestin-only pills (RR, 1.6; 95% CI, 1.0 –2.4) entailed similar levels of increased risk. An increased risk of borderline significance was found among short-term (i.e., less than 13 months) users before age 20 years (RR, 1.3; 95% CI, 1.0 –1.7) and before first full-term pregnancy (RR, 1.4; 95% CI, 1.0 –1.8).Longterm users of OCs were at a higher risk of breast cancer than never users (test for trend, P 0.005). Current/recent use of OCs is associated with an increased breast cancer risk. Use of combined OCs and progestinonly pills seem to increase the risk at the same level.

Introduction Use of hormonal contraceptives has revolutionized the reproductive life of women since the 1960s (1). Such drugscan be divided into combined OCs3 and progestin-only contraceptives, available as injections, implants, oral preparations (pills), and hormone-releasing intrauterine devices. OC is the common generic term for combined OCs and progestin-only pills when it is not specified which of the two is used. These contraceptives affect not only the reproductive system but also the incidence of variousdiseases, as reviewed recently (1). In particular, use of combined OCs has been reported to slightly increase breast cancer risk. The effect is highest among current users and vanishes within 10 years after cessation of use (2). With regard to use of progestin-only pills, the results are inconsistent, but there is some suggestion that the risk is slightly elevated in current and recent users (3). Mostdata on the association between use of combined OCs and breast cancer risk come from case-control studies (1, 3), which are susceptible to recall bias (1, 4). The association between combined OCs and breast cancer has also been analyzed in several cohort studies, particularly in relation to drugs used until the early 1980s (1, 2, 5–14). For the association between breast cancer and progestin-onlypills, there are a few case-control studies (15–17) and the pooled analysis of individual data made by the Collaborative Group on Hormonal Factors and Breast Cancer (3). We report here the first results from the Women’s Lifestyle and Health study, a large prospective cohort study that began in Norway and Sweden in the early 1990s. The study was specifically designed to examine the role of hormonal...