Angiotensin-converting enzyme inhibitors enhance the effect of cyclooxygenase inhibitors on breast cancer: A nationwide case-control study

Objectives: Angiotensin-converting enzyme (ACE) inhibitors are first-line antihypertensive and potential cancer preventive agents. Interest in breast cancer prevention is growing, and more clinical evidence is needed regarding the effects of preventive therapy, alone or in combination. Methods: This was a nationwide case-control analysis from the Taiwan National health Insurance Research Database. We analyzed 16 847 female breast cancer patients (diagnosed between 1 January 2002 and 31 December 2008) and 50 541 matched individuals. Longitudinal exposure to ACE inhibitors and cyclooxygenase inhibitors was compared. Results: The risk of developing breast cancer among patients taking both aspirin and an ACE inhibitor decreased as the ACE inhibitor dose increased. Among patients receiving between 28 and 364 cumulative defined daily doses (cDDDs) of aspirin, the adjusted odds ratios (ORs) were 0.97 (0.90-1.06), 0.91 (0.82-1.03), and 0.79 (0.68-0.92) for women taking ACE inhibitors for 0-27, 28-364, and more than 365 cDDD, respectively. Among women receiving more than 365 cDDD of aspirin, the adjusted ORs were 0.91 (0.80-1.03), 0.81 (0.70-0.94), and 0.81 (0.71-0.92) as the ACE inhibitor dose increased, respectively. Women taking nonaspirin NSAIDs along with an ACE inhibitor had the same finding. Among women taking 28-364 cDDD of NSAIDs, the adjusted ORs were 0.85 (0.81-0.89), 0.87 (0.81-0.94), and 0.80 (0.73-0.88); for women receiving more than 365 cDDD of NSAIDs, the adjusted ORs were 0.68 (0.62-0.74), 0.61 (0.53-0.70), and 0.60 (0.52-0.70) as the ACE inhibitor dose increased, respectively. Conclusion: The findings of this nationwide analysis support the hypothesis that ACE inhibitors enhance the antitumor effect of cyclooxygenase inhibitors on breast cancer.