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Non-steroidal anti-inflammatory drug use, hormone receptor status, and breast cancer-specific mortality in the Carolina Breast Cancer Study

  • Epidemiology
  • Published:
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Abstract

Epidemiologic studies report a protective association between non-steroidal anti-inflammatory drug (NSAID) use and hormone receptor-positive breast cancer risk, a finding consistent with NSAID-mediated suppression of aromatase-driven estrogen biosynthesis. However, the association between NSAID use and breast cancer-specific mortality is uncertain and it is unknown whether this relationship differs by hormone receptor status. This study comprised 935 invasive breast cancer cases, of which 490 were estrogen receptor (ER)-positive, enrolled between 1996 and 2001 in the Carolina Breast Cancer Study. Self-reported NSAID use in the decade prior to diagnosis was categorized by duration and regularity of use. Differences in tumor size, stage, node, and receptor status by NSAID use were examined using Chi-square tests. Associations between NSAID use and breast cancer-specific mortality were examined using age- and race-adjusted Cox proportional hazards analysis. Tumor characteristics did not differ by NSAID use. Increased duration and regularity of NSAID use was associated with reduced breast cancer-specific mortality in women with ER-positive tumors (long-term regular use (≥8 days/month for ≥ 3 years) versus no use; hazard ratio (HR) 0.48; 95 % confidence interval (CI) 0.23–0.98), with a statistically significant trend with increasing duration and regularity (p-trend = 0.036). There was no association for ER-negative cases (HR 1.19; 95 %CI 0.50–2.81; p-trend = 0.891). Long-term, regular NSAID use in the decade prior to breast cancer diagnosis was associated with reduced breast cancer-specific mortality in ER-positive cases. If confirmed, these findings support the hypothesis that potential chemopreventive properties of NSAIDs are mediated, at least in part, through suppression of estrogen biosynthesis.

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References

  1. Khuder SA, Mutgi AB (2001) Breast cancer and NSAID use: a meta-analysis. Br J Cancer 84:1188–1192

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. 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(1):28

    Article  PubMed Central  PubMed  Google Scholar 

  3. Takkouche B, Regueira-Mendez C, Etminan M (2008) Breast cancer and use of nonsteroidal anti-inflammatory drugs: a meta-analysis. J Natl Cancer Inst 100:1439–1447

    Article  CAS  PubMed  Google Scholar 

  4. Bosetti C, Rosato V, Gallus S et al (2012) Aspirin and cancer risk: a quantitative review to 2011. Ann Oncol 23:1403–1415

    Article  CAS  PubMed  Google Scholar 

  5. Luo T, Yan HM, He P et al (2012) Aspirin use and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 131:581–587

    Article  CAS  PubMed  Google Scholar 

  6. Moorman PG, Grubber JM, Millikan RC et al (2003) Association between non-steroidal anti-inflammatory drugs (NSAIDs) and invasive breast cancer and carcinoma in situ of the breast. Cancer Causes Control 14:915–922

    Article  PubMed  Google Scholar 

  7. 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. JAMA 29:2433–2440

    Article  Google Scholar 

  8. 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 97:805–812

    Article  CAS  PubMed  Google Scholar 

  9. Gill JK, Maskarinec G, Wilkens LR et al (2007) Nonsteroidal antiinflammatory drugs and breast cancer risk: the multiethnic cohort. Am J Epidemiol 166:1150–1158

    Article  PubMed  Google Scholar 

  10. Gierach GL, Lacey JV Jr, Schatzkin A et al (2008) Nonsteroidal anti-inflammatory drugs and breast cancer risk in the National Institutes of Health-AARP Diet and Health Study. Breast Cancer Res 10:R38

    Article  PubMed Central  PubMed  Google Scholar 

  11. Howe LR, Subbaramaiah K, Brown AM et al (2001) Cyclooxygenase-2: a target for the prevention and treatment of breast cancer. Endocr Relat Cancer 8:97–114

    Article  CAS  PubMed  Google Scholar 

  12. Zhao Y, Agarwal VR, Mendelson CR et al (1996) Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene. Endocrinology 137:5739–5742

    CAS  PubMed  Google Scholar 

  13. Holmes MD, Chen WY, Li L et al (2010) Aspirin intake and survival after breast cancer. J Clin Oncol 28:1467–1472

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Blair CK, Sweeney C, Anderson KE et al (2007) NSAID use and survival after breast cancer diagnosis in post-menopausal women. Breast Cancer Res Treat 101:191–197

    Article  CAS  PubMed  Google Scholar 

  15. Wernli KJ, Hampton JM, Trentham-Dietz A et al (2011) Use of antidepressants and NSAIDs in relation to mortality in long-term breast cancer survivors. Pharmacoepidemiol Drug Saf 20:131–137

    Article  PubMed Central  PubMed  Google Scholar 

  16. Li Y, Brasky TM, Nie J et al (2012) Use of nonsteroidal anti-inflammatory drugs and survival following breast cancer diagnosis. Cancer Epidemiol Biomark Prev 21:239–242

    Article  CAS  Google Scholar 

  17. Newman B, Moorman PG, Millikan R et al (1995) The Carolina Breast Cancer Study: integrating population-based epidemiology and molecular biology. Breast Cancer Res Treat 35:51–60

    Article  CAS  PubMed  Google Scholar 

  18. O’Brien KM, Cole SR, Tse CK et al (2010) Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina Breast Cancer Study. Clin Cancer Res 16:6100–6110

    Article  PubMed Central  PubMed  Google Scholar 

  19. Liu CH, Chang SH, Narko K et al (2001) Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem 276:18563–18569

    Article  CAS  PubMed  Google Scholar 

  20. Chang SH, Liu CH, Conway R et al (2004) Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression. Proc Natl Acad Sci USA 101:591–596

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Wang D, Dubois RN (2010) Eicosanoids and cancer. Nat Rev Cancer 10:181–193

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Hwang D, Scollard D, Byrne J et al (1998) Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J Natl Cancer Inst 90:455–460

    Article  CAS  PubMed  Google Scholar 

  23. Ristimaki A, Sivula A, Lundin J et al (2002) Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res 62:632–635

    CAS  PubMed  Google Scholar 

  24. Hudson AG, Gierach GL, Modugno F et al (2008) Nonsteroidal anti-inflammatory drug use and serum total estradiol in postmenopausal women. Cancer Epidemiol Biomark Prev 17:680–687

    Article  CAS  Google Scholar 

  25. Kirsh VA, Kreiger N, Cotterchio M et al (2007) Nonsteroidal antiinflammatory drug use and breast cancer risk: subgroup findings. Am J Epidemiol 166:709–716

    Article  PubMed  Google Scholar 

  26. 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. JAMA 294:47–55

    Article  CAS  PubMed  Google Scholar 

  27. Zhang Y, Coogan PF, Palmer JR et al (2005) Use of nonsteroidal antiinflammatory drugs and risk of breast cancer: the Case-Control Surveillance Study revisited. Am J Epidemiol 162:165–170

    Article  PubMed  Google Scholar 

  28. 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 Biomark Prev 14:261–264

    CAS  Google Scholar 

  29. Brasky TM, Bonner MR, Moysich KB et al (2011) Non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk: differences by molecular subtype. Cancer Causes Control 22:965–975

    Article  PubMed Central  PubMed  Google Scholar 

  30. Zhang SM, Cook NR, Manson JE et al (2008) Low-dose aspirin and breast cancer risk: results by tumour characteristics from a randomised trial. Br J Cancer 98:989–991

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Bardia A, Olson JE, Vachon CM et al (2011) Effect of aspirin and other NSAIDs on postmenopausal breast cancer incidence by hormone receptor status: results from a prospective cohort study. Breast Cancer Res Treat 126:149–155

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Patterson RE, Flatt SW, Saquib N et al (2010) Medical comorbidities predict mortality in women with a history of early stage breast cancer. Breast Cancer Res Treat 122:859–865

    Article  PubMed Central  PubMed  Google Scholar 

  33. Ji J, Liu X, Sundquist K et al (2011) Survival of cancer in patients with rheumatoid arthritis: a follow-up study in Sweden of patients hospitalized with rheumatoid arthritis 1 year before diagnosis of cancer. Rheumatology (Oxford) 50:1513–1518

    Article  Google Scholar 

  34. Chow LW, Yip AY, Loo WT et al (2008) Celecoxib anti-aromatase neoadjuvant (CAAN) trial for locally advanced breast cancer. J Steroid Biochem Mol Biol 111:13–17

    Article  CAS  PubMed  Google Scholar 

  35. Lustberg MB, Povoski SP, Zhao W et al (2011) Phase II trial of neoadjuvant exemestane in combination with celecoxib in postmenopausal women who have breast cancer. Clin Breast Cancer 11:221–227

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Bresalier RS, Sandler RS, Quan H et al (2005) Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352:1092–1102

    Article  CAS  PubMed  Google Scholar 

  37. Solomon SD, McMurray JJ, Pfeffer MA et al (2005) Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 352:1071–1080

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest

The authors declare that they have no conflicts of interest.

Funding

This work was supported by a SPORE in Breast Cancer [P50-CA058223] and the University Cancer Research Fund, University of North Carolina at Chapel Hill.

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Authors and Affiliations

  1. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    E. H. Allott, A. F. Olshan, L. A. Carey & M. A. Troester

  2. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    E. H. Allott, C.-K. Tse, A. F. Olshan & M. A. Troester

  3. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    L. A. Carey

  4. Department of Community and Family Medicine, Duke University Medical Center, Durham, NC, USA

    P. G. Moorman

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  1. E. H. Allott
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  2. C.-K. Tse
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  3. A. F. Olshan
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  4. L. A. Carey
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  6. M. A. Troester
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Correspondence to M. A. Troester.

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Allott, E.H., Tse, CK., Olshan, A.F. et al. Non-steroidal anti-inflammatory drug use, hormone receptor status, and breast cancer-specific mortality in the Carolina Breast Cancer Study. Breast Cancer Res Treat 147, 415–421 (2014). https://doi.org/10.1007/s10549-014-3099-z

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  • DOI: https://doi.org/10.1007/s10549-014-3099-z

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