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Correlates of circulating C-reactive protein and serum amyloid A concentrations in breast cancer survivors

  • Epidemiology
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Introduction Inflammatory status may be an important prognostic factor for breast cancer. Correlates of markers of inflammation in breast cancer survivors have not been thoroughly evaluated. Methods Using data from, the Health, Eating, Activity, and Lifestyle (HEAL) Study (a population-based, multiethnic prospective cohort study of female breast cancer patients) we evaluated the associations between circulating markers of inflammation (C-reactive protein [CRP] and serum amyloid A [SAA], measured ∼31 months after diagnosis) and several demographic, lifestyle, and clinical characteristics in 741 disease-free breast cancer survivors. Analysis of variance and regression methods were used for statistical analyses of log-transformed values of CRP and SAA. Results After adjusting for age, BMI, ethnicity, and study site, higher concentrations of CRP were associated with increasing concentration of SAA (P-trend < 0.0001), increasing age (P-trend < 0.0001), increasing BMI (P-trend < 0.0001), increasing waist circumference (P-trend < 0.0001), positive history of heart failure (P = 0.0007), decreasing physical activity (P-trend = 0.005), Hispanic ethnicity (P = 0.05 vs. non-Hispanic white), and current smoking (P = 0.03 vs. never smoking). Vitamin E supplementation (P = 0.0005), tamoxifen use (P = 0.008), and radiation treatment (compared to no chemotherapy or radiation; P = 0.04) were associated with reduced CRP. Associations of CRP with clinical characteristics were not significant in the adjusted models. In a multivariate analysis, CRP showed significant associations with waist circumference, BMI, age, history of heart failure, tamoxifen use, and vitamin E supplementation (R2 = 0.35). Similar, yet fewer, associations were observed for SAA (R2 = 0.19). Conclusions This study highlights important correlates of inflammatory status in breast cancer patients. Our results are consistent with those from similar studies of healthy women.

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References

  1. Kuller LH, Tracy RP, Shaten J et al (1996) Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Multiple risk factor intervention trial. Am J Epidemiol 144(6):537–547

    PubMed  CAS  Google Scholar 

  2. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867

    Article  PubMed  CAS  Google Scholar 

  3. Thun MJ, Henley SJ, Patrono C (2002) Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst 94(4):252–266

    PubMed  CAS  Google Scholar 

  4. Sandler RS, Halabi S, Baron JA et al (2003) A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. New Engl J Med 348(10):883–890

    Article  PubMed  CAS  Google Scholar 

  5. Baron JA, Cole BF, Sandler RS et al (2003) A randomized trial of aspirin to prevent colorectal adenomas. New Engl J Med 348(10):891–899

    Article  PubMed  CAS  Google Scholar 

  6. 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 

  7. Ulrich CM, Bigler J, Potter JD (2006) Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils, and pharmacogenetics. Nat Rev Cancer 6(2):130–140

    Article  PubMed  CAS  Google Scholar 

  8. Schultz DR, Arnold PI (1990) Properties of four acute phase proteins: C-reactive protein, serum amyloid A protein, alpha 1-acid glycoprotein, and fibrinogen. Semin Arthritis Rheum 20(3):129–147

    Article  PubMed  CAS  Google Scholar 

  9. Uhlar CM, Whitehead AS (1999) Serum amyloid A, the major vertebrate acute-phase reactant. Eur J Biochem 265(2):501–523

    Article  PubMed  CAS  Google Scholar 

  10. Manley PN, Ancsin JB, Kisilevsky R (2006) Rapid recycling of cholesterol: the joint biologic role of C-reactive protein and serum amyloid A. Med Hypotheses 66(4):784–792

    Article  PubMed  CAS  Google Scholar 

  11. McArdle PA, Mir K, Almushatat AS et al (2006) Systemic inflammatory response, prostate-specific antigen and survival in patients with metastatic prostate cancer. Urol Int 77(2):127–129

    Article  PubMed  CAS  Google Scholar 

  12. Crumley AB, McMillan DC, McKernan M et al (2006) An elevated C-reactive protein concentration, prior to surgery, predicts poor cancer-specific survival in patients undergoing resection for gastro-oesophageal cancer. Br J Cancer 94(11):1568–1571

    PubMed  CAS  Google Scholar 

  13. Wong VK, Malik HZ, Hamady ZZ et al (2007) C-reactive protein as a predictor of prognosis following curative resection for colorectal liver metastases. Br J Cancer 96(2):222–225

    Article  PubMed  CAS  Google Scholar 

  14. McMillan DC, Canna K, McArdle CS (2003) Systemic inflammatory response predicts survival following curative resection of colorectal cancer. Br J Surg 90(2):215–219

    Article  PubMed  CAS  Google Scholar 

  15. Scott HR, McMillan DC, Forrest LM et al (2002) The systemic inflammatory response, weight loss, performance status and survival in patients with inoperable non-small cell lung cancer. Br J Cancer 87(3):264–267

    Article  PubMed  CAS  Google Scholar 

  16. Barber MD, Powell JJ, Lynch SF et al (1999) Two polymorphisms of the tumour necrosis factor gene do not influence survival in pancreatic cancer. Clin Exp Immunol 117(3):425–429

    Article  PubMed  CAS  Google Scholar 

  17. O’Hanlon DM, Lynch J, Cormican M et al (2002) The acute phase response in breast carcinoma. Anticancer Res 22(2B):1289–1293

    PubMed  Google Scholar 

  18. Blann AD, Byrne GJ, Baildam AD (2002) Increased soluble intercellular adhesion molecule-1, breast cancer and the acute phase response. Blood Coagul Fibrinolysis 13(2):165–168

    Article  PubMed  CAS  Google Scholar 

  19. Heikkila K, Ebrahim S, Rumley A et al (2007) Associations of circulating C-reactive protein and Interleukin-6 with survival in women with and without cancer: findings from the British women’s heart and health study. Cancer Epidemiol Biomarkers Prev 16(6):1155–1159

    Article  PubMed  CAS  Google Scholar 

  20. Hooning MJ, Botma A, Aleman BM et al (2007) Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst 99(5):365–375

    Article  PubMed  Google Scholar 

  21. Danesh J, Whincup P, Walker M et al (2000) Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 321(7255):199–204

    Article  PubMed  CAS  Google Scholar 

  22. Visser M, Bouter LM, McQuillan GM et al (1999) Elevated C-reactive protein levels in overweight and obese adults [see comments]. Jama 282(22):2131–2135

    Article  PubMed  CAS  Google Scholar 

  23. Geffken DF, Cushman M, Burke GL et al (2001) Association between physical activity and markers of inflammation in a healthy elderly population. Am J Epidemiol 153(3):242–250

    Article  PubMed  CAS  Google Scholar 

  24. Abramson JL, Vaccarino V (2002) Relationship between physical activity and inflammation among apparently healthy middle-aged and older US adults. Arch Intern Med 162(11):1286–1292

    Article  PubMed  Google Scholar 

  25. LaMonte MJ, Durstine JL, Yanowitz FG et al (2002) Cardiorespiratory fitness and C-reactive protein among a tri-ethnic sample of women. Circulation 106(4):403–406

    Article  PubMed  CAS  Google Scholar 

  26. Pitsavos C, Chrysohoou C, Panagiotakos DB et al (2003) Association of leisure-time physical activity on inflammation markers (C-reactive protein, white cell blood count, serum amyloid A, and fibrinogen) in healthy subjects (from the ATTICA study). Am J Cardiol 91(3):368–370

    Article  PubMed  CAS  Google Scholar 

  27. Mohamed-Ali V, Goodrick S, Rawesh A et al (1997) Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 82(12):4196–4200

    Article  PubMed  CAS  Google Scholar 

  28. Tchernof A, Nolan A, Sites CK et al (2002) Weight loss reduces C-reactive protein levels in obese postmenopausal women. Circulation 105(5):564–569

    Article  PubMed  Google Scholar 

  29. Smith JK, Dykes R, Douglas JE et al (1999) Long-term exercise and atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease. JAMA 281(18):1722–1727

    Article  PubMed  CAS  Google Scholar 

  30. Gielen S, Adams V, Mobius-Winkler S et al (2003) Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure.[comment]. J Am Coll Cardiol 42(5):861–868

    Article  PubMed  CAS  Google Scholar 

  31. Wener MH, Daum PR, McQuillan GM (2000) The influence of age, sex, and race on the upper reference limit of serum C-reactive protein concentration. J Rheumatol 27(10):2351–2359

    PubMed  CAS  Google Scholar 

  32. Prasad K (2006) C-reactive protein (CRP)-lowering agents. Cardiovasc Drug Rev 24(1):33–50

    Article  PubMed  CAS  Google Scholar 

  33. Al Murri AM, Bartlett JM, Canney PA et al (2006) Evaluation of an inflammation-based prognostic score (GPS) in patients with metastatic breast cancer. Br J Cancer 94(2):227–230

    Article  PubMed  CAS  Google Scholar 

  34. Al Murri AM, Wilson C, Lannigan A et al (2007) Evaluation of the relationship between the systemic inflammatory response and cancer-specific survival in patients with primary operable breast cancer. Br J Cancer 96(6):891–895

    Article  PubMed  CAS  Google Scholar 

  35. McShane LM, Altman DG, Sauerbrei W et al (2006) REporting recommendations for tumor MARKer prognostic studies (REMARK). Breast Cancer Res Treat 100(2):229–235

    Article  PubMed  Google Scholar 

  36. Irwin ML, Crumley D, McTiernan A et al (2003) Physical activity levels before and after a diagnosis of breast carcinoma: the Health, Eating, Activity, and Lifestyle (HEAL) study. Cancer 97(7):1746–1757

    Article  PubMed  Google Scholar 

  37. Irwin ML, McTiernan A, Bernstein L et al (2004) Physical activity levels among breast cancer survivors. Med Sci Sports Exerc 36(9):1484–1491

    PubMed  Google Scholar 

  38. McTiernan A, Rajan KB, Tworoger SS et al (2003) Adiposity and sex hormones in postmenopausal breast cancer survivors. J Clin Oncol 21(10):1961–1966

    Article  PubMed  CAS  Google Scholar 

  39. Ledue TB, Weiner DL, Sipe JD et al (1998) Analytical evaluation of particle-enhanced immunonephelometric assays for C-reactive protein, serum amyloid A and mannose-binding protein in human serum. Ann Clin Biochem 35(Pt 6):745–753

    PubMed  CAS  Google Scholar 

  40. Khera A, McGuire DK, Murphy SA et al (2005) Race and gender differences in C-reactive protein levels. J Am Coll Cardiol 46(3):464–469

    Article  PubMed  CAS  Google Scholar 

  41. Yanbaeva DG, Dentener MA, Creutzberg EC et al (2007) Systemic effects of smoking. Chest 131(5):1557–1566

    Article  PubMed  CAS  Google Scholar 

  42. Fairey AS, Courneya KS, Field CJ et al (2005) Effect of exercise training on C-reactive protein in postmenopausal breast cancer survivors: a randomized controlled trial. Brain Behav Immun 19(5):381–388

    Article  PubMed  CAS  Google Scholar 

  43. Singh U, Jialal I (2004) Anti-inflammatory effects of alpha-tocopherol. Ann N Y Acad Sci 1031:195–203

    Article  PubMed  CAS  Google Scholar 

  44. Devaraj S, Jialal I (2000) Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and type 2 diabetic patients. Free Radic Biol Med 29(8):790–792

    Article  PubMed  CAS  Google Scholar 

  45. Upritchard JE, Sutherland WH, Mann JI (2000) Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in type 2 diabetes. Diabetes Care 23(6):733–738

    Article  PubMed  CAS  Google Scholar 

  46. Murphy RT, Foley JB, Tome MT et al (2004) Vitamin E modulation of C-reactive protein in smokers with acute coronary syndromes. Free Radic Biol Med 36(8):959–965

    Article  PubMed  CAS  Google Scholar 

  47. Bonanni B, Johansson H, Gandini S et al (2003) Effect of tamoxifen at low doses on ultrasensitive C-reactive protein in healthy women. J Thromb Haemost 1(10):2149–2152

    Article  PubMed  CAS  Google Scholar 

  48. Cushman M, Costantino JP, Tracy RP et al (2001) Tamoxifen and cardiac risk factors in healthy women: suggestion of an anti-inflammatory effect. Arterioscler Thromb Vasc Biol 21(2):255–261

    PubMed  CAS  Google Scholar 

  49. Dietrich M, Jialal I (2005) The effect of weight loss on a stable biomarker of inflammation, C-reactive protein. Nutr Rev 63(1):22–28

    Article  PubMed  Google Scholar 

  50. Plaisance EP, Grandjean PW (2006) Physical activity and high-sensitivity C-reactive protein. Sports Med 36(5):443–458

    Article  PubMed  Google Scholar 

  51. Ryu SY, Kim CB, Nam CM et al (2001) Is body mass index the prognostic factor in breast cancer?: a meta-analysis. J Korean Med Sci 16(5):610–614

    PubMed  CAS  Google Scholar 

  52. Majed B, Moreau T, Senouci K et al (2007) Is obesity an independent prognosis factor in woman breast cancer? Breast Cancer Res Treat (Online publication ahead of print)

  53. La Guardia M, Giammanco M (2001) Breast cancer and obesity. Panminerva Med 43(2):123–133

    PubMed  CAS  Google Scholar 

  54. Kasapis C, Thompson PD (2005) The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. J Am Coll Cardiol 45(10):1563–1569

    Article  PubMed  CAS  Google Scholar 

  55. Abrahamson PE, Gammon MD, Lund MJ et al (2006) Recreational physical activity and survival among young women with breast cancer. Cancer 107(8):1777–1785

    Article  PubMed  Google Scholar 

  56. Holmes MD, Chen WY, Feskanich D et al (2005) Physical activity and survival after breast cancer diagnosis. JAMA 293(20):2479–2486

    Article  PubMed  CAS  Google Scholar 

  57. Borugian MJ, Sheps SB, Kim-Sing C et al (2004) Insulin, macronutrient intake, and physical activity: are potential indicators of insulin resistance associated with mortality from breast cancer? Cancer Epidemiol Biomarkers Prev 13(7):1163–1172

    PubMed  CAS  Google Scholar 

  58. Enger SM, Bernstein L (2004) Exercise activity, body size and premenopausal breast cancer survival. Br J Cancer 90(11):2138–2141

    PubMed  CAS  Google Scholar 

  59. Rohan TE, Fu W, Hiller JE (1995) Physical activity and survival from breast cancer. Eur J Cancer Prev 4(5):419–424

    Article  PubMed  CAS  Google Scholar 

  60. Hoffman-Goetz L, Apter D, Demark-Wahnefried W et al (1998) Possible mechanisms mediating an association between physical activity and breast cancer. Cancer 83(3 Suppl):621–628

    Article  PubMed  CAS  Google Scholar 

  61. Licastro F, Candore G, Lio D et al (2005) Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immun Ageing 2:8

    Article  PubMed  CAS  Google Scholar 

  62. Yancik R, Wesley MN, Ries LA et al (2001) Effect of age and comorbidity in postmenopausal breast cancer patients aged 55 years and older. JAMA 285(7):885–892

    Article  PubMed  CAS  Google Scholar 

  63. Yankaskas BC (2005) Epidemiology of breast cancer in young women. Breast Dis 23:3–8

    PubMed  Google Scholar 

  64. Althuis MD, Brogan DD, Coates RJ et al (2003) Breast cancers among very young premenopausal women (United States). Cancer Causes Control 14(2):151–160

    Article  PubMed  Google Scholar 

  65. Yu GP, Ostroff JS, Zhang ZF et al (1997) Smoking history and cancer patient survival: a hospital cancer registry study. Cancer Detect Prev 21(6):497–509

    PubMed  CAS  Google Scholar 

  66. Manjer J, Andersson I, Berglund G et al (2000) Survival of women with breast cancer in relation to smoking. Eur J Surg 166(11):852–858

    Article  PubMed  CAS  Google Scholar 

  67. Holmes MD, Murin S, Chen WY et al (2007) Smoking and survival after breast cancer diagnosis. Int J Cancer 120(12):2672–2677

    Article  PubMed  CAS  Google Scholar 

  68. Ewertz M, Gillanders S, Meyer L et al (1991) Survival of breast cancer patients in relation to factors which affect the risk of developing breast cancer. Int J Cancer 49(4):526–530

    Article  PubMed  CAS  Google Scholar 

  69. Murin S, Pinkerton KE, Hubbard NE et al (2004) The effect of cigarette smoke exposure on pulmonary metastatic disease in a murine model of metastatic breast cancer. Chest 125(4):1467–1471

    Article  PubMed  Google Scholar 

  70. Early Breast Cancer Trialists’ Collaborative Group (1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351(9114):1451–1467

    Article  Google Scholar 

  71. Decensi A, Robertson C, Viale G et al (2003) A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers. J Natl Cancer Inst 95(11):779–790

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The Authors would like to thank Dr. Peter Campbell and Dr. Kristen Campbell for their helpful comments related to this manuscript, and the HEAL participants for their ongoing dedication to this study. This study was supported through National Cancer Institute contracts N01-CN-75036–20, NO1-CN-05228, NO1-PC-67010, U54-CA116847 and training grant R25-CA94880. A portion of this work was conducted through the Clinical Research Center at the University of Washington and supported by the National Institutes of Health grant M01-RR-00037, and University of New Mexico grant, NCRR M01-RR-0997. Data collection for the Women’s CARE Study at the University of Southern California was supported by contract N01-HD-3-3175 from the National Institute of Child Health and Human Development and patient identification was supported in part by contract 050Q-8709-S1528 from the California Department of Health Services.

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Correspondence to Cornelia M. Ulrich.

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Pierce, B.L., Neuhouser, M.L., Wener, M.H. et al. Correlates of circulating C-reactive protein and serum amyloid A concentrations in breast cancer survivors. Breast Cancer Res Treat 114, 155–167 (2009). https://doi.org/10.1007/s10549-008-9985-5

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