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

Lee, Hsiu-Haoa,b; Tsan, Yu-Tsea,c,d; Ho, Wen-Chaoe; Lin, Meng-Hunge; Lee, Chang-Hsingf; Tseng, Chuen-Deng; Guo, Yue-Leona; Wang, Jung-Derh; Chen, Pau-ChungaHealth Data Analysis in Taiwan (hDATa) Research Group

doi: 10.1097/HJH.0b013e328358d42f
ORIGINAL PAPERS: Therapeutic aspects

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.

aInstitution of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health

bDepartment of Internal Medicine, Taipei City Hospital, Zhongxing Branch, Taipei

cDivision of Toxicology, Department of Emergency Medicine, Taichung Veterans General Hospital

dSchool of Medicine, Chung Shan Medical University

eDepartment of Public Health, China Medical University, Taichung

fDepartment of Occupational Medicine, Ton Yen General Hospital, Hisn-Chu County

gDivision of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei

hDepartment of Public Health, National Cheng Kung University College of Medicine, Tainan, Taiwan

Correspondence to Pau-Chung Chen, MD, PhD, Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, 17, Syujhou Road, Taipei 1 10055, Taiwan. Tel: +886 2 3366 8088; fax: +886 2 2358 2402; e-mail:

Abbreviations: ACE, angiotensin-converting enzyme; BNHI, Bureau of NHI; cDDD, cumulative defined daily dose; CI, confidence interval; COX, cyclooxygenase; IQR, interquartile range; NHI, National Health Insurance; OR, odds ratio; PI3, phosphatidylinositol 3-kinase; VEGF, vascular endothelial growth factor

Received 25 February, 2012

Revised 31 July, 2012

Accepted 2 August, 2012

© 2012 Lippincott Williams & Wilkins, Inc.