This systematic review and meta-analysis examined the association between oral contraceptive use and breast cancer risk in 6,390,250 women without baseline breast cancer from 16 prospective cohort studies, with at least 5 years of follow-up. The analysis compared ever users of oral contraceptives to never users, with the primary outcome being breast cancer risk.
Ever use of oral contraceptives was not significantly associated with breast cancer risk, with a pooled hazard ratio of 1.03 (95% CI: 0.99, 1.07; 95% prediction interval: 0.91, 1.16). The dose-response analysis, examining risk per decade of oral contraceptive use across six studies, showed a non-significant hazard ratio increase of 1.06 per decade (95% CI: 0.97, 1.16). However, when one study was excluded from this analysis, the dose-response relationship became statistically significant (HR 1.11 per decade, p < 0.01).
Safety and tolerability data were not reported in the meta-analysis. A key limitation is that the dose-response analysis was based on only six studies, limiting its robustness. The authors note that the findings represent association, not causation, and the main pooled result was not statistically significant.
For clinical practice, these observational data suggest no significant overall association between oral contraceptive use and breast cancer risk in this large population. However, the inconsistent dose-response findings and study limitations warrant cautious interpretation when discussing contraceptive options with patients.
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OBJECTIVES: 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.
METHODS: 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.
RESULTS: 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 ( < 0.01).
CONCLUSION: 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.