Association between Proton Pump Inhibitors (PPIs) Use and Risk of Breast Cancer: A Systematic Review and Meta-analysis

Abstract

Background and objective: Proton pump inhibitors (PPIs) are widely prescribed for acid-related gastrointestinal disorders, but recent studies have raised concerns about their potential long-term effects, including cancer risk. The association between PPI use and breast cancer remains unclear, with conflicting results reported across observational studies. This systematic review and meta-analysis aim to find the association between the risk of breast cancer and PPI use compared to non-users.

Methods: A comprehensive search of major databases was conducted up to April 2026 to identify relevant case-control and cohort studies. After the study selection process, appropriate data were extracted to evaluate potential associations. A random-effects model was employed to estimate the hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CIs).

Results: Six observational studies (three cohort and three case–control) were included. In cohort studies, meta-analysis showed no statistically significant association between PPI use and breast cancer risk (HR: 0.73, 95% CI 0.52–1.04; p = 0.083), although the point estimate suggested a modest reduction in risk among PPI users compared with non-users. In case–control studies, the pooled analysis also indicated no significant association (OR: 0.88, 95% CI 0.75–1.04; p = 0.133).

Conclusion: This meta-analysis of observational studies found no statistically significant association between PPI use and breast cancer risk, although a slight, non-significant trend toward reduced risk was observed. Further large, methodologically robust prospective studies are needed to confirm whether a modest protective effect exists and to refine risk–benefit assessments for long-term PPI therapy.