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Association between NSAIDs use and breast cancer risk: a systematic review and meta-analysis

  • Epidemiology
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Abstract

The association between non-steroidal anti-inflammatory drugs (NSAIDs) use and breast cancer has remained controversial. Therefore, an overall quantitative estimate of the association needs to be studied. A systematic review and meta-analysis was executed to explore the pooled estimate for relative risk (RR) and 95% confidence interval (CI) using random or fixed effects models based on heterogeneity analysis. Overall 26 studies with 528,705 participants were included. The RR of NSAIDs use and the incidence of breast cancer was 0.94 (95% CI: 0.88–1.00) with random effects model. A slight reduction of breast cancer by taking aspirin and ibuprofen was both observed with pooled RR of 0.91 (95% CI: 0.83–0.98) and 0.81 (95% CI: 0.67–0.97), respectively. Our results indicate that NSAIDs use is associated with a slight decrease for the development of breast cancer with a marginally statistical significant difference. The associations are slightly more obvious in aspirin and ibuprofen use.

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References

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57(1):43–66

    Article  PubMed  Google Scholar 

  2. Malachi T, Chaimoff C, Feller N, Halbrecht I (1981) Prostaglandin E2 and cyclic AMP in tumor and plasma of breast cancer patients. J Cancer Res Clin Oncol 102(1):71–79. doi:10.1007/BF00410536

    Article  PubMed  CAS  Google Scholar 

  3. Watson J, Chuah SY (1985) Prostaglandins, steroids and human mammary cancer. Eur J Cancer Clin Oncol 21(9):1051–1055. doi:10.1016/0277-5379(85)90290-1

    Article  PubMed  CAS  Google Scholar 

  4. Kune GA, Kune S, Watson LF (1988) Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne colorectal cancer study. Cancer Res 48(15):4399–4404

    PubMed  CAS  Google Scholar 

  5. Suh O, Mettlin C, Petrelli NJ (1993) Aspirin use, cancer, and polyps of the large bowel. Cancer 72(4):1171–1177. doi :10.1002/1097-0142(19930815)72:4<1171::AID-CNCR2820720407>3.0.CO;2-D

    Article  PubMed  CAS  Google Scholar 

  6. Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC (1994) Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med 121(4):241–246

    PubMed  CAS  Google Scholar 

  7. Giovannucci E, Egan KM, Hunter DJ et al (1995) Aspirin and the risk of colorectal cancer in women. N Engl J Med 333(10):609–614. doi:10.1056/NEJM199509073331001

    Article  PubMed  CAS  Google Scholar 

  8. Kahn HS, Tatham LM, Thun MJ, Heath CW Jr (1998) Risk factors for self-reported colon polyps. J Gen Intern Med 13(5):303–310. doi:10.1046/j.1525-1497.1998.00095.x

    Article  PubMed  CAS  Google Scholar 

  9. Slattery ML, Samowitz W, Hoffman M, Ma KN, Levin TR, Neuhausen S (2004) Aspirin, NSAIDs, and colorectal cancer: possible involvement in an insulin-related pathway. Cancer Epidemiol Biomarkers Prev 13(4):538–545

    PubMed  CAS  Google Scholar 

  10. Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Curhan GC, Fuchs CS (2005) Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. J Am Med Assoc 294(8):914–923. doi:10.1001/jama.294.8.914

    Article  CAS  Google Scholar 

  11. Dube C, Rostom A, Lewin G et al (2007) The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the U.S. preventive services task force. Ann Intern Med 146(5):365–375

    PubMed  Google Scholar 

  12. Gonzalez-Perez A, Garcia Rodriguez LA, Lopez-Ridaura R (2003) Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis. BMC Cancer 3:28

    Article  PubMed  Google Scholar 

  13. Khuder SA, Mutgi AB (2001) Breast cancer and NSAID use: a meta-analysis. Br J Cancer 84(9):1188–1192. doi:10.1054/bjoc.2000.1709

    Article  PubMed  CAS  Google Scholar 

  14. Mangiapane S, Blettner M, Schlattmann P (2008) Aspirin use and breast cancer risk: a meta-analysis and meta-regression of observational studies from 2001 to 2005. Pharmacoepidemiol Drug Saf 17(2):115–124. doi:10.1002/pds.1503

    Article  PubMed  Google Scholar 

  15. Cook NR, Lee IM, Gaziano JM et al (2005) Low-dose aspirin in the primary prevention of cancer: the Women’s Health Study: a randomized controlled trial. J Am Med Assoc 294(1):47–55. doi:10.1001/jama.294.1.47

    Article  CAS  Google Scholar 

  16. Gaudet MM, Gammon MD, Santella RM et al (2005) MnSOD Val-9Ala genotype, pro- and anti-oxidant environmental modifiers, and breast cancer among women on long Island, New York. Cancer Causes Control 16(10):1225–1234. doi:10.1007/s10552-005-0375-6

    Article  PubMed  Google Scholar 

  17. Rahme E, Ghosn J, Dasgupta K, Rajan R, Hudson M (2005) Association between frequent use of nonsteroidal anti-inflammatory drugs and breast cancer. BMC Cancer 5:159

    Article  PubMed  CAS  Google Scholar 

  18. Stevens VL, Rodriguez C, Pavluck AL, Thun MJ, Calle EE (2006) Association of polymorphisms in the paraoxonase 1 gene with breast cancer incidence in the CPS-II nutrition cohort. Cancer Epidemiol Biomarkers Prev 15(6):1226–1228. doi:10.1158/1055-9965.EPI-05-0930

    Article  PubMed  CAS  Google Scholar 

  19. Moorman PG, Sesay J, Nwosu V et al (2005) Cyclooxygenase 2 polymorphism (Val511Ala), nonsteroidal anti-inflammatory drug use and breast cancer in African American women. Cancer Epidemiol Biomarkers Prev 14(12):3013–3014. doi:10.1158/1055-9965.EPI-05-0291

    Article  PubMed  CAS  Google Scholar 

  20. Harris RE, Beebe-Donk J, Alshafie GA (2006) Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX-2) inhibitors. BMC Cancer 6:27

    Article  PubMed  CAS  Google Scholar 

  21. Shen J, Gammon MD, Terry MB, Teitelbaum SL, Neugut AI, Santella RM (2006) Genetic polymorphisms in the cyclooxygenase-2 gene, use of nonsteroidal anti-inflammatory drugs, and breast cancer risk. Breast Cancer Res 8(6):R71. doi:10.1186/bcr1629

    Article  PubMed  Google Scholar 

  22. Gallicchio L, McSorley MA, Newschaffer CJ et al (2006) Nonsteroidal antiinflammatory drugs, cyclooxygenase polymorphisms, and the risk of developing breast carcinoma among women with benign breast disease. Cancer 106(7):1443–1452. doi:10.1002/cncr.21763

    Article  PubMed  CAS  Google Scholar 

  23. Vogel U, Christensen J, Nexø BA, Wallin H, Friis S, Tjønneland A (2007) Peroxisome profilerator-activated receptorg2 Pro12Ala, interaction with alcohol intake and NSAID use, in relation to risk of breast cancer in a prospective study of Danes. Carcinogenesis 28(2):427–434. doi:10.1093/carcin/bgl170

    Article  PubMed  CAS  Google Scholar 

  24. Blair CK, Sweeney C, Anderson KE, Folsom AR (2007) NSAID use and survival after breast cancer diagnosis in post-menopausal women. Breast Cancer Res Treat 101(2):191–197. doi:10.1007/s10549-006-9277-x

    Article  PubMed  CAS  Google Scholar 

  25. Slattery ML, Curtin K, Baumgartner R et al (2007) IL6, aspirin, nonsteroidal anti-inflammatory drugs, and breast cancer risk in women living in the southwestern United States. Cancer Epidemiol Biomarkers Prev 16(4):747–755. doi:10.1158/1055-9965.EPI-06-0667

    Article  PubMed  CAS  Google Scholar 

  26. Gallicchio L, Visvanathan K, Burke A, Hoffman SC, Helzlsouer KJ (2007) Nonsteroidal anti-inflammatory drugs and the risk of developing breast cancer in a population-based prospective cohort study in Washington County, MD. Int J Cancer 121(1):211–215. doi:10.1002/ijc.22656

    Article  PubMed  CAS  Google Scholar 

  27. Kirsh VA, Kreiger N, Cotterchio M, Sloan M, Theis B (2007) Nonsteroidal antiinflammatory drug use and breast cancer risk: subgroup findings. Am J Epidemiol 166(6):709–716. doi:10.1093/aje/kwm216

    Article  PubMed  Google Scholar 

  28. Jacobs EJ, Thun MJ, Bain ER, Rodriguez C, Henley SJ, Calle EE (2007) A large cohort study of long term daily use of adult-strength aspirin and cancer incidence. J Natl Cancer Inst 99:608–615

    Article  PubMed  CAS  Google Scholar 

  29. Kwan ML, Habel LA, Slattery ML, Caan B (2007) NSAIDs and breast cancer recurrence in a prospective cohort study. Cancer Causes Control 18(6):613–620. doi:10.1007/s10552-007-9003-y

    Article  PubMed  Google Scholar 

  30. Gill JK, Maskarinec G, Wilkens LR, Pike MC, Henderson BE, Kolonel LN (2007) Nonsteroidal antiinflammatory drugs and breast cancer risk: the multiethnic cohort. Am J Epidemiol 166(10):1150–1158. doi:10.1093/aje/kwm195

    Article  PubMed  Google Scholar 

  31. Harris RE, Beebe-Donk J, Alshafie GA (2007) Cancer chemoprevention by cyclooxygenase 2 (COX-2) blockade: results of case control studies. Subcell Biochem 42:193–212

    Article  PubMed  Google Scholar 

  32. Davis S, Mirick DK (2007) Medication use and the risk of breast cancer. Eur J Epidemiol 22(5):319–325. doi:10.1007/s10654-007-9135-0

    Article  PubMed  Google Scholar 

  33. Ready A, Velicer CM, McTiernan A, White E (2008) NSAID use and breast cancer risk in the VITAL cohort. Breast Cancer Res Treat 109(3):533–543. doi:10.1007/s10549-007-9665-x

    Article  PubMed  CAS  Google Scholar 

  34. Zhang SM, Cook NR, Manson JE, Lee IM, Buring JE (2008) Low-dose aspirin and breast cancer risk: results by tumour characteristics from a randomised trial. Br J Cancer 98(5):989–991. doi:10.1038/sj.bjc.6604240

    Article  PubMed  CAS  Google Scholar 

  35. Friis S, Thomassen L, Sorensen HT et al (2008) Nonsteroidal anti-inflammatory drug use and breast cancer risk: a Danish cohort study. Eur J Cancer Prev 17(2):88–96

    Article  PubMed  Google Scholar 

  36. Bax L, Yu LM, Ikeda N, Tsuruta H, Moons KGM (2008) MIX: comprehensive free software for meta-analysis of causal research data. Version 1.7. http://mix-for-meta-analysis.info

  37. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. doi:10.1136/bmj.327.7414.557

    Article  PubMed  Google Scholar 

  38. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101. doi:10.2307/2533446

    Article  PubMed  CAS  Google Scholar 

  39. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    PubMed  CAS  Google Scholar 

  40. Duval S, Tweedie R (2000) Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56(2):455–463. doi:10.1111/j.0006-341X.2000.00455.x

    Article  PubMed  CAS  Google Scholar 

  41. Friedman GD, Ury HK (1980) Initial screening for carcinogenicity of commonly used drugs. J Natl Cancer Inst 65(4):723–733

    PubMed  CAS  Google Scholar 

  42. Thun MJ, Namboodri MM, Calle EE, Flanders WD, Heath C Jr (1993) Aspirin use and risk of fetal cancer. Cancer Res 53:1322–1327

    PubMed  CAS  Google Scholar 

  43. Rosenberg L (1995) Nonsteroidal anti-inflammatory drugs and cancer. Prev Med 24(2):107–109. doi:10.1006/pmed.1995.1018

    Article  PubMed  CAS  Google Scholar 

  44. Egan KM, Stampfer MJ, Giovannucci E, Rosner BA, Colditz GA (1996) Prospective study of regular aspirin use and the risk of breast cancer. J Natl Cancer Inst 88(14):988–993. doi:10.1093/jnci/88.14.988

    Article  PubMed  CAS  Google Scholar 

  45. Marshall SF, Bernstein L, Anton-Culver H et al (2005) Nonsteroidal anti-inflammatory drug use and breast cancer risk by stage and hormone receptor status. J Natl Cancer Inst 97(11):805–812

    Article  PubMed  CAS  Google Scholar 

  46. Garcia Rodriguez LA, Gonzalez-Perez A (2004) Risk of breast cancer among users of aspirin and other anti-inflammatory drugs. Br J Cancer 91(3):525–529. doi:10.1038/sj.bjc.6602003

    Article  PubMed  CAS  Google Scholar 

  47. Friis S, Sorensen HT, McLaughlin JK, Johnsen SP, Blot WJ, Olsen JH (2003) A population-based cohort study of the risk of colorectal and other cancers among users of low-dose aspirin. Br J Cancer 88(5):684–688. doi:10.1038/sj.bjc.6600760

    Article  PubMed  CAS  Google Scholar 

  48. Sorensen HT, Friis S, Norgard B et al (2003) Risk of cancer in a large cohort of nonaspirin NSAID users: a population-based study. Br J Cancer 88(11):1687–1692. doi:10.1038/sj.bjc.6600945

    Article  PubMed  CAS  Google Scholar 

  49. Swede H, Mirand AL, Menezes RJ, Moysich KB (2005) Association of regular aspirin use and breast cancer risk. Oncology 68(1):40–47. doi:10.1159/000084818

    Article  PubMed  CAS  Google Scholar 

  50. Harris RE, Namboodiri K, Stellman SD, Wynder EL (1995) Breast cancer and NSAID use: heterogeneity of effect in a case–control study. Prev Med 24(2):119–120. doi:10.1006/pmed.1995.1022

    Article  PubMed  CAS  Google Scholar 

  51. Neugut AI, Rosenberg DJ, Ahsan H et al (1998) Association between coronary heart disease and cancers of the breast, prostate, and colon. Cancer Epidemiol Biomarkers Prev 7(10):869–873

    PubMed  CAS  Google Scholar 

  52. Coogan PF, Rao SR, Rosenberg L et al (1999) The relationship of nonsteroidal anti-inflammatory drug use to the risk of breast cancer. Prev Med 29(2):72–76. doi:10.1006/pmed.1999.0518

    Article  PubMed  CAS  Google Scholar 

  53. Langman MJ, Cheng KK, Gilman EA, Lancashire RJ (2000) Effect of anti-inflammatory drugs on overall risk of common cancer: case–control study in general practice research database. BMJ 320(7250):1642–1646. doi:10.1136/bmj.320.7250.1642

    Article  PubMed  CAS  Google Scholar 

  54. Harris RE, Namboodiri KK, Farrar WB (1996) Nonsteroidal antiinflammatory drugs and breast cancer. Epidemiology 7(2):203–205. doi:10.1097/00001648-199603000-00017

    Article  PubMed  CAS  Google Scholar 

  55. Sharpe CR, Collet JP, McNutt M, Belzile E, Boivin JF, Hanley JA (2000) Nested case–control study of the effects of non-steroidal anti-inflammatory drugs on breast cancer risk and stage. Br J Cancer 83(1):112–120. doi:10.1054/bjoc.2000.1119

    Article  PubMed  CAS  Google Scholar 

  56. Cotterchio M, Kreiger N, Sloan M, Steingart A (2001) Nonsteroidal anti-inflammatory drug use and breast cancer risk. Cancer Epidemiol Biomarkers Prev 10(11):1213–1217

    PubMed  CAS  Google Scholar 

  57. Meier CR, Schmitz S, Jick H (2002) Association between acetaminophen or nonsteroidal anti-inflammatory drugs and risk of developing ovarian, breast, or colon cancer. Pharmacotherapy 22(3):303–309. doi:10.1592/phco.22.5.303.33189

    Article  PubMed  CAS  Google Scholar 

  58. Moorman PG, Grubber JM, Millikan RC, Newman B (2003) Association between non-steroidal anti-inflammatory drugs (NSAIDs) and invasive breast cancer and carcinoma in situ of the breast. Cancer Causes Control 14(10):915–922. doi:10.1023/B:CACO.0000007973.59863.66

    Article  PubMed  Google Scholar 

  59. Terry MB, Gammon MD, Zhang FF et al (2004) Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. J Am Med Assoc 291(20):2433–2440. doi:10.1001/jama.291.20.2433

    Article  CAS  Google Scholar 

  60. Paganini-Hill A, Chao A, Ross RK, Henderson BE (1989) Aspirin use and chronic diseases: a cohort study of the elderly. BMJ 299(6710):1247–1250

    Article  PubMed  CAS  Google Scholar 

  61. Harris RE, Kasbari S, Farrar WB (1999) Prospective study of nonsteroidal anti-inflammatory drugs and breast cancer. Oncol Rep 6(1):71–73

    PubMed  CAS  Google Scholar 

  62. Schreinemachers DM, Everson RB (1994) Aspirin use and lung, colon, and breast cancer incidence in a prospective study. Epidemiology 5(2):138–146. doi:10.1097/00001648-199403000-00003

    Article  PubMed  CAS  Google Scholar 

  63. Johnson TW, Anderson KE, Lazovich D, Folsom AR (2002) Association of aspirin and nonsteroidal anti-inflammatory drug use with breast cancer. Cancer Epidemiol Biomarkers Prev 11(12):1586–1591

    PubMed  CAS  Google Scholar 

  64. Harris RE, Chlebowski RT, Jackson RD et al (2003) Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women’s Health Initiative. Cancer Res 63(18):6096–6101

    PubMed  CAS  Google Scholar 

  65. Jacobs EJ, Thun MJ, Connell CJ et al (2005) Aspirin and other nonsteroidal anti-inflammatory drugs and breast cancer incidence in a large U.S. cohort. Cancer Epidemiol Biomarkers Prev 14(1):261–264

    PubMed  CAS  Google Scholar 

  66. Zhang Y, Coogan PF, Palmer JR, Strom BL, Rosenberg L (2005) Use of nonsteroidal antiinflammatory drugs and risk of breast cancer: the case–control surveillance study revisited. Am J Epidemiol 162(2):165–170. doi:10.1093/aje/kwi182

    Article  PubMed  Google Scholar 

  67. Parrett ML, Harris RE, Joarder FS, Ross MS, Clausen KP, Robertson FM (1997) Cyclooxygenase-2 gene expression in human breast cancer. Int J Oncol 10:503–507

    CAS  Google Scholar 

  68. Yoshimura N, Sano H, Okamoto M et al (2003) Expression of cyclooxygenase-1 and -2 in human breast cancer. Surg Today 33(11):805–811. doi:10.1007/s00595-003-2606-3

    Article  PubMed  CAS  Google Scholar 

  69. Silverstein FE, Faich G, Goldstein JL, Tatham LM, La Vecchia C (2000) Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial Celecoxib Long-term Arthritis Safety Study. J Am Med Assoc 284:1247–1255

    Article  CAS  Google Scholar 

  70. Bombardier C, Laine L, Reicin A, Tatham LM, Vecchia CL (2000) Group VIGORS: comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 343:1520–1528

    Article  PubMed  CAS  Google Scholar 

  71. Veronesi U, Boyle P, Goldhirsch A, Orecchia R, Viale G (2005) Breast cancer. Lancet 365(9472):1727–1741. doi:10.1016/S0140-6736(05)66546-4

    Article  PubMed  Google Scholar 

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Zhao, Ys., Zhu, S., Li, Xw. et al. Association between NSAIDs use and breast cancer risk: a systematic review and meta-analysis. Breast Cancer Res Treat 117, 141–150 (2009). https://doi.org/10.1007/s10549-008-0228-6

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