Oral contraceptives use and breast cancer risk: a systematic review and meta-analysis of prospective cohort studies

Controversy persists regarding the association between oral contraceptives (OCs) use and breast cancer risk, with inconsistent findings from prior cohort studies. This study aimed to synthesise evidence on OCs use and breast cancer risk, including dose-response relationships.
Databases (PubMed, Embase, Web of Science) were searched through March 2025 for related prospective cohort studies. Eligibility criteria included female participants without baseline breast cancer, comparison of ever OCs users vs. never users, reported hazard ratio (HR) with 95% confidence interval (CI), and at least 5 years of follow-up. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effects model was used to pool effect sizes, and a two-stage dose-response meta-analysis evaluated associations per decade of OCs use. Sensitivity analyses and publication bias tests were conducted.
Sixteen studies (6,390,250 women; 104,070 breast cancer cases) were included. Pooled HR for OCs users vs. non-users was 1.03 (95% CI: 0.99, 1.07), with a 95% prediction interval (PI): 0.91, 1.16. Sensitivity analyses confirmed consistency, and no publication bias was detected for sixteen studies. Initial dose-response meta-analysis (6 studies) showed a non-significant 6% HR increase per decade use (exp[coefficient] = 1.06, 95% CI: 0.97, 1.16), with a 95% PI: 0.80, 1.41. Excluding one study by Dumeaux et al. revealed a significant 11% increase (p < 0.01).
Based on sixteen studies, OCs ever-users were not significantly associated with breast cancer risk. Based on six limited studies, no strong dose-response relationship that warrants special attention has been identified.