Advertisement

Medical Oncology

, 30:432 | Cite as

Pretreatment neutrophil/lymphocyte ratio is superior to platelet/lymphocyte ratio as a predictor of long-term mortality in breast cancer patients

  • Basem Azab
  • Neeraj Shah
  • Jared Radbel
  • Pamela Tan
  • Vijaya Bhatt
  • Steven Vonfrolio
  • Ayman Habeshy
  • Antonio Picon
  • Scott Bloom
Original Paper

Abstract

The aim of our study was to assess the predictive value of platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) in terms of survival in breast cancer patients. This is an observational study of 437 breast cancer patients treated between January 2004 and December 2006. Survival status was obtained from our cancer registry and Social Security Death Index. Survival analysis, stratified by NLR and PLR quartiles, was used to evaluate their prognostic values. Patients in the highest 4th PLR and NLR quartiles had higher 5-year mortality rate (30.4 and 40.3 %) compared to those in the lower three PLR and NLR quartiles (12.1 and 8.2 %), p < 0.0001. Multivariate hazard ratios of 4th PLR and NLR quartiles compared to first PLR and NLR quartiles were 3.68 (1.74–7.77, p = 0.001) and 3.67 (1.52–8.86, p = 0.004). Higher PLR only showed a trend of higher mortality in patients with normal lymphocyte count, whereas NLR continued to be statistically significant predictor of 5-year mortality in all lymphocyte count subsets. Pretreatment NLR is an independent predictor of long-term mortality in breast cancer patients, whereas pretreatment PLR was not superior to absolute lymphocyte count alone in predicting long-term mortality.

Keywords

PLR NLR Neutrophil–lymphocyte ratio Platelet–lymphocyte ratio Breast cancer Mortality 

Notes

Conflict of interest

Authors have no conflict of interest to report.

References

  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.PubMedCrossRefGoogle Scholar
  2. 2.
    Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357:539–45.PubMedCrossRefGoogle Scholar
  3. 3.
    Mantovani A, Marchesi F, Porta C, et al. Inflammation and cancer: breast cancer as a prototype. Breast. 2007;16:S27–33.PubMedCrossRefGoogle Scholar
  4. 4.
    Queen M, Ryan R, Holzer R, et al. Breast cancer cells stimulate neutrophils to produce oncostatin M: potential implications for tumor progression. Cancer Res. 2005;65:8896–904.PubMedCrossRefGoogle Scholar
  5. 5.
    Pierce BL, Ballard-Barbash R, Berstein L, et al. Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol. 2009;21:3437–44.CrossRefGoogle Scholar
  6. 6.
    Bachelot T, Ray-Coquard I, Menetrier-Caux C, et al. Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients. Br J Cancer. 2003;88:1721–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Al Murri AM, Bartlett JM, Canney PA, et al. Evaluation of an inflammation-based prognostic score (GPS) in patients with metastatic breast cancer. Br J Cancer. 2006;94:227–30.PubMedCrossRefGoogle Scholar
  8. 8.
    Schmidt H, Suciu S, Punt CJ, Gore M, Kruit W, Patel P, Lienard D, von der Maase H, Eggermont AM. American Joint Committee on Cancer stage IV Melanoma; EORTC 18951. Pretreatment levels of peripheral neutrophils and leukocytes as independent predictors of overall survival in patients with American Joint Committee on Cancer Stage IV Melanoma: results of the EORTC 18951 Biochemotherapy Trial. J Clin Oncol. 2007;25(12):1562–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Teramukai S, Kitano T, Kishida Y, Kawahara M, Kubota K, Komuta K, Minato K, Mio T, Fujita Y, Yonei T, Nakano K, Tsuboi M, Shibata K, Furuse K, Fukushima M. Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: an analysis of Japan Multinational Trial Organisation LC00-03. Eur J Cancer. 2009;45(11):1950–8. [Epub 2009 Feb 21].PubMedCrossRefGoogle Scholar
  10. 10.
    Lin MS, Huang JX, Zhu JY, et al. Elevation of Platelet Count in Patients with Colorectal Cancer Predicts Tendency to Metastases and Poor Prognosis. Hepatogastroenterology. 2012;59. doi: 10.5754/hge12277.
  11. 11.
    Fogar P, Sperti C, Basso D, et al. Decreased total lymphocyte counts in pancreatic cancer: an index of adverse outcome. Pancreas. 2006;32:22–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, Tredan O, Verweij J, Biron P, Labidi I, Guastalla JP, Bachelot T, Perol D, Chabaud S, Hogendoorn PC, Cassier P, Dufresne A. European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009;69(13):5383–91. [Epub 2009 Jun 23].PubMedCrossRefGoogle Scholar
  13. 13.
    Halazun K, Hardy M, Rana A, et al. Negative impact of neutrophil–lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma. Ann Surg. 2009;250:141–51.PubMedCrossRefGoogle Scholar
  14. 14.
    Sarraf K, Belcher E, Raevsky E, et al. Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer. J Thorac Cardiovasc Surg. 2009;137:425–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Yamanaka T, Matsumoto S, Teramukai S, et al. The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in advanced gastric cancer. Oncology. 2007;73:215–20.PubMedCrossRefGoogle Scholar
  16. 16.
    Kishi Y, Kopetz S, Chun Y, et al. Blood neutrophil-to-lymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy. Ann Surg Oncol. 2009;16:614–22.PubMedCrossRefGoogle Scholar
  17. 17.
    Chiang SF, Hung HY, Tang R, Changchien CR, Chen JS, You YT, Chiang JM, Lin JR. Can neutrophil-to-lymphocyte ratio predict the survival of colorectal cancer patients who have received curative surgery electively? Int J Colorectal Dis. 2012 [Epub ahead of print].Google Scholar
  18. 18.
    Keizman D, Ish-Shalom M, Huang P, Eisenberger MA, Pili R, Hammers H, Carducci MA. The association of pre-treatment neutrophil to lymphocyte ratio with response rate, progression free survival and overall survival of patients treated with sunitinib for metastatic renal cell carcinoma. Eur J Cancer. 2012;48(2):202–8. [Epub 2011 Oct 19].PubMedCrossRefGoogle Scholar
  19. 19.
    Tomita M, Shimizu T, Ayabe T, Yonei A, Onitsuka T. Preoperative neutrophil to lymphocyte ratio as a prognostic predictor after curative resection for non-small cell lung cancer. Anticancer Res. 2011;31(9):2995–8.PubMedGoogle Scholar
  20. 20.
    Jung MR, Park YK, Jeong O, Seon JW, Ryu SY, Kim DY, Kim YJ. Elevated preoperative neutrophil to lymphocyte ratio predicts poor survival following resection in late stage gastric cancer. J Surg Oncol. 2011;104(5):504–10. doi: 10.1002/jso.21986 [Epub 2011 May 25].PubMedCrossRefGoogle Scholar
  21. 21.
    Gomez D, Farid S, Malik HZ, Young AL, Toogood GJ, Lodge JP, Prasad KR. Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma. World J Surg. 2008;32(8):1757–62.PubMedCrossRefGoogle Scholar
  22. 22.
    Shimada H, Takiguchi N, Kainuma O, Soda H, Ikeda A, Cho A, Miyazaki A, Gunji H, Yamamoto H, Nagata M. High preoperative neutrophil–lymphocyte ratio predicts poor survival in patients with gastric cancer. Gastric Cancer. 2010;13(3):170–6. [Epub 2010 Sep 5].PubMedCrossRefGoogle Scholar
  23. 23.
    Cho H, Hur HW, Kim SW, Kim SH, Kim JH, Kim YT, Lee K. Pre-treatment neutrophil to lymphocyte ratio is elevated in epithelial ovarian cancer and predicts survival after treatment. Cancer Immunol Immunother. 2009;58(1):15–23. [Epub 2008 Apr 15].PubMedCrossRefGoogle Scholar
  24. 24.
    Garcea G, Ladwa N, Neal CP, Metcalfe MS, Dennison AR, Berry DP. Preoperative neutrophil-to-lymphocyte ratio (NLR) is associated with reduced disease-free survival following curative resection of pancreatic adenocarcinoma. World J Surg. 2011;35(4):868–72.PubMedCrossRefGoogle Scholar
  25. 25.
    Smith R, Bosonnet L, Raraty M, et al. Preoperative platelet–lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma. Am J Surg. 2009;197:466–72.PubMedCrossRefGoogle Scholar
  26. 26.
    Smith R, Ghaneh P, Sutton R, et al. Prognosis of resected ampullary adenocarcinoma by preoperative serum CA 19–9 levels and platelet-lymphocyte ratio. J Gastrointest Surg. 2008;12:1422–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Kwon HC, Kim SH, Oh SY, Lee S, Lee JH, Choi HJ, Park KJ, Roh MS, Kim SG, Kim HJ, Lee JH. Clinical significance of preoperative neutrophil–lymphocyte versus platelet–lymphocyte ratio in patients with operable colorectal cancer. Biomarkers. 2012;17(3):216–22. [Epub 2012 Mar 17].PubMedCrossRefGoogle Scholar
  28. 28.
    Asher V, Lee J, Innamaa A, et al. Preoperative platelet lymphocyte ratio as an independent prognostic marker in ovarian cancer. Clin Transl Oncol. 2011;13:499–503.PubMedCrossRefGoogle Scholar
  29. 29.
    Azab B, Bhatt V, Phookhan J, et al. Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients. Ann Surg Oncol. 2012;19:217–24.PubMedCrossRefGoogle Scholar
  30. 30.
    Bhatti I, Peacock O, Lloyd G, et al. Preoperative hematological markers as independent predictors of prognosis in resected pancreatic ductal adenocarcinoma: neutrophil–lymphocyte versus platelet–lymphocyte ratio. Am J Surg. 2010;200:197–203.PubMedCrossRefGoogle Scholar
  31. 31.
    Rakoff-Nahoum S. Why cancer and inflammation? Yale J Biol Med. 2006;79(3–4):123–30.PubMedGoogle Scholar
  32. 32.
    Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Bambace NM, Holmes CE. The platelet contribution to cancer progression. J Thromb Haemost. 2011;9:237–49.PubMedCrossRefGoogle Scholar
  34. 34.
    Dvorak HF, Brown LF, Detmar M, et al. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995;146:1029–39.PubMedGoogle Scholar
  35. 35.
    Benoy I, Salgado R, Colpaert C, et al. Serum interleukin 6, plasma VEGF, serum VEGF, and VEGF platelet load in breast cancer patients. Clin Breast Cancer. 2002;2:311–5.PubMedCrossRefGoogle Scholar
  36. 36.
    Wiesner T, Bugl S, Mayer F, et al. Differential changes in platelet VEGF, Tsp, CXCL12, and CXCL4 in patients with metastatic cancer. Clin Exp Metastasis. 2010;27:141–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3(6):453–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Brown KM, Domin C, Aranha GV, Yong S, Shoup M. Increased preoperative platelet count is associated with decreased survival after resection for adenocarcinoma of the pancreas. Am J Surg. 2005;189(3):278–82.PubMedCrossRefGoogle Scholar
  39. 39.
    Holmes CE, Levis JE, Ornstein DL. Activated platelets enhance ovarian cell invasion in a cellular model of metastasis. Clin Exp Metastasis. 2009;26:653–61.PubMedCrossRefGoogle Scholar
  40. 40.
    De Larco JE, Wuertz BRK, Furcht LT. The potential role of neutrophils in promoting the metastatic phenotype of tumors releasing interleukin-8. Clin Cancer Res. 2004;10:4895–900.PubMedCrossRefGoogle Scholar
  41. 41.
    Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, Ochoa AC. Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res. 2009;69(4):1553–60. [Epub 2009 Feb 5].PubMedCrossRefGoogle Scholar
  42. 42.
    Müller I, Munder M, Kropf P, Hänsch GM. Polymorphonuclear neutrophils and T lymphocytes: strange bedfellows or brothers in arms? Trends Immunol. 2009;30(11):522–30. [Epub 2009 Sep 21].PubMedCrossRefGoogle Scholar
  43. 43.
    Petrie HT, Klassen LW, Kay HD. Inhibition of human Cytotoxic T lymphocyte activity in vitro By autologous peripheral blood granulocytes. J Immunol. 1985;134:230–4.PubMedGoogle Scholar
  44. 44.
    Queen MM, Ryan RE, Holzer RG, Keller-Peck CR, Jorcyk CL. Breast cancer cells stimulate neutrophils to produce oncostatin M: potential implications for tumor progression. Cancer Res. 2005;65(19):8896–904.PubMedCrossRefGoogle Scholar
  45. 45.
    Atzpodien J, Royston P, Wandert T. DGCIN—German Cooperative Renal Carcinoma Chemo-Immunotherapy Trials Group. Metastatic renal carcinoma comprehensive prognostic system. Br J Cancer. 2003;88(3):348–53.PubMedCrossRefGoogle Scholar
  46. 46.
    Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21:137–48.PubMedCrossRefGoogle Scholar
  47. 47.
    Niederhuber JE. Cancer vaccines: the molecular basis for T cell killing of tumor cells. Oncologist. 1997;2(5):280–3.PubMedGoogle Scholar
  48. 48.
    Strand S, Galle PR. Immune evasion by tumours: involvement of the CD95 (APO-1/Fas) system and its clinical implications. Mol Med Today. 1998;4(2):63–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, Rosenberg SA. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. 2006;314(5796):126–9. Epub 2006 Aug 31.PubMedCrossRefGoogle Scholar
  50. 50.
    Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH, Ellis IO, Green AR. Tumor-infiltrating CD8 + lymphocytes predict clinical outcome in breast cancer. J Clin Oncol. 2011;29(15):1949–55. Epub 2011 Apr 11.PubMedCrossRefGoogle Scholar
  51. 51.
    West NR, Milne K, Truong PT, Macpherson N, Nelson BH, Watson PH. Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer. Breast Cancer Res. 2011;13(6):R126. [Epub 2011 Dec 8].PubMedCrossRefGoogle Scholar
  52. 52.
    Khorana AA, Fine RL. Pancreatic cancer and thromboembolic disease. Lancet Oncol. 2004;5(11):655–63.PubMedCrossRefGoogle Scholar
  53. 53.
    Zacharski LR, Memoli VA, Ornstein DL, Rousseau SM, Kisiel W, Kudryk BJ. Tumor cell procoagulant and urokinase expression in carcinoma of the ovary. J Natl Cancer Inst. 1993;85(15):1225–30.PubMedCrossRefGoogle Scholar
  54. 54.
    Khorana AA, Ahrendt SA, Ryan CK, Francis CW, Hruban RH, Hu YC, Hostetter G, Harvey J, Taubman MB. Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer. Clin Cancer Res. 2007;13(10):2870–5.PubMedCrossRefGoogle Scholar
  55. 55.
    Menczer J, Schejter E, Geva D, Ginath S, Zakut H. Ovarian carcinoma associated thrombocytosis. Correlation with prognostic factors and with survival. Eur J Gynaecol Oncol. 1998;19(1):82–4.PubMedGoogle Scholar
  56. 56.
    Kim SJ, Choi IK, Park KH, Yoon SY, Oh SC, Seo JH, Choi CW, Kim BS, Shin SW, Kim YH, Kim JS. Serum vascular endothelial growth factor per platelet count in hepatocellular carcinoma: correlations with clinical parameters and survival. Jpn J Clin Oncol. 2004;34(4):184–90.PubMedCrossRefGoogle Scholar
  57. 57.
    Kusumanto YH, Dam WA, Hospers GAP, et al. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis. 2003;6:283–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Basem Azab
    • 1
  • Neeraj Shah
    • 2
  • Jared Radbel
    • 2
  • Pamela Tan
    • 1
  • Vijaya Bhatt
    • 2
  • Steven Vonfrolio
    • 1
  • Ayman Habeshy
    • 1
  • Antonio Picon
    • 1
  • Scott Bloom
    • 1
  1. 1.Department of SurgeryStaten Island University HospitalStaten IslandUSA
  2. 2.Department of Internal MedicineStaten Island University HospitalStaten IslandUSA

Personalised recommendations