Negative Association of Proton Pump Inhibitors With Subsequent Development of Breast Cancer: A Nationwide Population‐Based Study

: Although current evidence suggests potential antitumor activity of proton pump inhibitors (PPIs), there is no population-based evidence of an association between PPI use and subsequent breast cancer risks. We used an observational case-control study to examine the association between prior PPI use and breast cancer occurrence. Additional analysis examined dose-response and age-stratified associations of PPIs with breast cancer. This study used data from the Taiwan National Health Insurance Research Dataset. A total of 64,234 women diagnosed with breast cancer between 2004 and in 2013 were selected as cases. Controls were 64,234 women without cancer who were selected by matching them with cases on the basis of sociodemographic characteristics and widely prevalent comorbidities. Each study subject's claims data were tracked back for 5 years to determine precancer prescriptions of PPIs. Logistic regression modeling was used for the analysis. A total of 11,871 (9.24%) women had used PPIs within the prior 5 years, 8.06% and 10.42% among cases and controls, respectively. Breast cancer patients were 25% less likely to have had prior PPI exposure after adjustment for comorbidities that predispose to PPI exposure (95%CI 0.72-0.78) in the risk of breast cancer occurrence. A dose-response effect was also detected, with the highest effect, 35% lower PPI odds (95%CI 0.61-0.70) among patients in the highest exposure category. Our findings may suggest that women at a higher-than-average risk of breast cancer may benefit from PPI prescriptions if they have medical conditions that could benefit from PPIs.