Breast Cancer Research and Treatment

, Volume 146, Issue 2, pp 439–446 | Cite as

Use of nonsteroidal anti-inflammatory drugs and reduced breast cancer risk among overweight women

  • Yong Cui
  • Sandra L. Deming-Halverson
  • Martha J. Shrubsole
  • Alicia Beeghly-Fadiel
  • Hui Cai
  • Alecia M. Fair
  • Xiao-Ou Shu
  • Wei ZhengEmail author


Chronic inflammation is associated with increased risk of multiple cancers, including breast cancer. Adipose tissues produce proinflammatory cytokines, and obesity is a risk factor for postmenopausal breast cancer. We evaluated the association of regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) with breast cancer risk, overall and by body mass index (BMI) and tumor subtypes defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. We conducted a population-based, case-control study involving 5,078 women aged 25-75 years who were recruited primarily from the Nashville metropolitan area of Tennessee. Multivariate unconditional logistic regression models were used to estimate odds ratios and 95 % confidence intervals for breast cancer risk after adjusting for multiple potential confounding factors. Regular use of any NSAID was associated with significantly reduced breast cancer risk (OR 0.78; 95 % CI 0.69–0.89). This association was observed for regular use of baby aspirin only (OR 0.82, 95 % CI 0.69–0.99), other NSAIDs only (OR 0.81, 95 % CI 0.69–0.95), and both baby aspirin and other NSAIDs (OR 0.52, 95 % CI 0.40–0.69). These significant inverse associations were found among overweight women (BMI ≥25 kg/m2) overall and by subtypes of breast cancer, but not among women with BMI <25 kg/m2 (P for interaction = 0.023). Regular use of NSAIDs was inversely associated with breast cancer risk, particularly among overweight women. Overweight women may benefit more from the protective effects of NSAID use than normal-weight women.


NSAIDs Obesity Breast cancer Epidemiology 



This work was supported by a research grant (R01CA100374) from the US National Cancer Institute. Surveys for this study were conducted by the Biospecimen and Survey Shared Resource, which is supported in part by P30CA68485. The authors would like to thank the study participants and research staff of the Nashville Breast Health Study for their support of this research, as well as Mary Jo Daly, Bethanie Rammer, and Kimberly Kreth for editing and preparing the manuscript. All experiments comply with the current laws of the United States of America.

Conflict of interest

The authors declare no conflicts of interest.


  1. 1.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454(7203):436–444. doi: 10.1038/nature07205 PubMedCrossRefGoogle Scholar
  3. 3.
    Hanahan D, Weinberg PA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi: 10.1016/j/cell.2011.02.013 PubMedCrossRefGoogle Scholar
  4. 4.
    Thun MJ, Blackard B (2009) Pharmacologic effects of NSAIDs and implications for the risks and benefits of long-term prophylactic use of aspirin to prevent cancer. Recent Results Cancer Res 181:215–221PubMedCrossRefGoogle Scholar
  5. 5.
    Elwood PC, Gallagher AM, Duthie GG, Mur LA, Morgan G (2009) Aspirin, salicylates, and cancer. Lancet 373(9671):1301–1309. doi: 10.1016/S0140-6736(09)60243-9 PubMedCrossRefGoogle Scholar
  6. 6.
    Taketo MM (1998) Cyclooxygenase-2 inhibit tumorigenesis (part I). J Natl Cancer Inst 90(20):1529–1536PubMedCrossRefGoogle Scholar
  7. 7.
    Park JY, Pillinger MH, Abramson SB (2006) Prostagladin E2 synthesis and secretion: the role of PGE2 synthases. Clin Immunol 119(3):229–240PubMedCrossRefGoogle Scholar
  8. 8.
    Howe LR (2007) Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer. Breast Cancer Res 9(4):210PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Ristimaki A, Sivula A, Lundin J, Lundin M, Salminen T, Haglund C, Joensuu H, Isola J (2002) Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res 62(3):632–635PubMedGoogle Scholar
  10. 10.
    Wang D, Dubois RN (2010) Eicosanoids and cancer. Nat Rev Cancer 10(3):181–193. doi: 10.1038/nrc2809 PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Terry MB, Gammon MD, Zhang FF, Tawfik H, Teitelbaum SL, Britton JA, Subbaramaiah K, Dannenberg AJ, Neugut AI (2004) Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA 291(20):2433–2440PubMedCrossRefGoogle Scholar
  12. 12.
    Takkouche B, Regueira-Méndez C, Etminan M (2008) Breast cancer and use of nonsteroidal anti-inflammatory drugs: a meta-analysis. J Natl Cancer Inst 100(20):1439–1447. doi: 10.1093/jnci/djn324 PubMedCrossRefGoogle Scholar
  13. 13.
    Luo T, Yan HM, He P, Lou Y, Yang YF, Zheng H (2012) Aspirin use and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 131(2):581–587. doi: 10.1007/s10549-011-1747-0 PubMedCrossRefGoogle Scholar
  14. 14.
    Wellen KE, Hotamisligil GS (2003) Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 112(12):1785–1788PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Fantuzzi G (2005) Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 115(9):911–919PubMedCrossRefGoogle Scholar
  16. 16.
    Ramos-Nino ME (2013) The role of chronic inflammation in obesity-associated cancers. ISRN Oncol 2013:697521. doi: 10.1155/2013/697521 PubMedCentralPubMedGoogle Scholar
  17. 17.
    Morris PG, Zhou XK, Milne GL, Goldstein D, Hawks LC, Dang CT, Modi S, Fornier MN, Hudis CA, Dannenberg AJ (2013) Increased levels of urinary PGE-M, a biomarker of inflammation, occur in association with obesity, aging, and lung metastases in patients with breast cancer. Cancer Prev Res (Phila) 6(5):428–436. doi: 10.1158/1940-6207.CAPR-12-0431 CrossRefGoogle Scholar
  18. 18.
    Subbaramaiah K, Morris PG, Zhou XK, Morrow M, Du B, Giri D, Kopelovich L, Hudis CA, Dannenberg AJ (2012) (2012) Increased levels of COX-2 and prostaglandin E2 contribute to elevated aromatase expression in inflamed breast tissue of obese women. Cancer Discov 2(4):356–365. doi: 10.1158/2159-8290.CD-11-0241 PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    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):1150–1158PubMedCrossRefGoogle Scholar
  20. 20.
    Gierach GL, Lacey JV Jr, Schatzkin A, Leitzmann MF, Richesson D, Hollenbeck AR, Brinton LA (2008) Nonsteroidal anti-inflammatory drugs and breast cancer risk in the National Institutes of Health-AARP Diet and Health Study. Breast Cancer Res 10(2):R38. doi: 10.1186/bcr2089 PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    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):211–215CrossRefGoogle Scholar
  22. 22.
    Bardia A, Olson JE, Vachon CM, Lazovich D, Vierkant RA, Wang AH, Limburg PJ, Anderson KE, Cerhan JR (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(1):149–155. doi: 10.1007/s10549-010-1074-x PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    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):165–170PubMedCrossRefGoogle Scholar
  24. 24.
    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):709–716PubMedCrossRefGoogle Scholar
  25. 25.
    Marshall SF, Bernstein L, Anton-Culver H, Deapen D, Horn-Ross PL, Mohrenweiser H, Peel D, Pinder R, Purdie DM, Reynolds P, Stram D, West D, Wright WE, Ziogas A, Ross RK (2005) Nonsteroidal anti-inflammatory drug use and breast cancer risk by stage and hormone receptor status. J Natl Cancer Inst 97(11):805–812PubMedCrossRefGoogle Scholar
  26. 26.
    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 PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Brasky TM, Bonner MR, Moysich KB, Ambrosone CB, Nie J, Tao MH, Edge SB, Kallakury BV, Marian C, Goerlitz DS, Trevisan M, Shields PG, Freudenheim JL (2011) Non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk: differences by molecular subtype. Cancer Causes Control 22(7):965–975. doi: 10.1007/s10552-011-9769-9 PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Zhang X, Smith-Warner SA, Collins LC, Rosner B, Willett WC, Hankinson SE (2012) Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and postmenopausal breast cancer incidence. J Clin Oncol 30(28):3468–3477PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    van Kruijsdijk RCM, van der Wall E, Visseren FL (2009) Obesity and Cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomark Prev 18(10):2569–2578. doi: 10.1158/1055-9965.EPI-09-0372 CrossRefGoogle Scholar
  30. 30.
    Harris RE, Chlebowski RT, Jackson RD, Frid DJ, Ascenseo JL, Anderson G, Loar A, Rodabough RJ, White E, McTiernan A, Initiative Women’s Health (2003) Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women’s Health Initiative. Cancer Res 63(18):6096–6101PubMedGoogle Scholar
  31. 31.
    Parise CA, Bauer KR, Brown MM, Caggiano V (2009) Breast cancer subtypes as defined by the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor2 (HER2) among women with invasive breast cancer in California, 1999-2004. Breast J 15(6):593–602. doi: 10.1111/j.1524-4741.2009.00822.x PubMedCrossRefGoogle Scholar
  32. 32.
    Chlebowski RT, Chen Z, Anderson GL, Rohan T, Aragaki A, Lane D, Dolan NC, Paskett ED, McTiernan A, Hubbell FA, Adams-Campbell LL, Prentice R (2005) Ethnicity and breast cancer: factors influencing differences in incidence and outcome. J Natl Cancer Inst 97(6):439–448PubMedCrossRefGoogle Scholar
  33. 33.
    Liu Y, Diamant AL, Thind A, Maly RC (2010) Validity of self-reports of breast cancer treatment in low-income, medically underserved women with breast cancer. Breast Cancer Res Treat 119(3):745–751. doi: 10.1007/s10549-009-0447-5 PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Maunsell E, Drolet M, Ouhoummane N, Robert J (2005) Breast cancer survivors accurately reported key treatment and prognostic characteristics. J Clin Epidemiol 58(4):364–369PubMedCrossRefGoogle Scholar
  35. 35.
    Schootman M, Jeffe DB, West MM, Aft R (2005) Self-report by elderly breast cancer patients was an acceptable alternative to surveillance, epidemiology, and end results (SEER) abstract data. J Clin Epidemiol 58(12):1316–1319PubMedCrossRefGoogle Scholar
  36. 36.
    Phillips KA, Milne RL, Buys S, Friedlander ML, Ward JH, McCredie MR, Giles GG, Hopper JL (2005) Agreement between self-reported breast cancer treatment and medical records in a population-based Breast Cancer Family Registry. J Clin Oncol 23(21):4679–4686PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Yong Cui
    • 1
  • Sandra L. Deming-Halverson
    • 1
  • Martha J. Shrubsole
    • 1
  • Alicia Beeghly-Fadiel
    • 1
  • Hui Cai
    • 1
  • Alecia M. Fair
    • 2
  • Xiao-Ou Shu
    • 1
  • Wei Zheng
    • 1
    Email author
  1. 1.Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer CenterVanderbilt University School of MedicineNashvilleUSA
  2. 2.Vanderbilt Institute for Clinical Translational ResearchVanderbilt University School of MedicineNashvilleUSA

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