The neutrophil-to-lymphocyte ratio: a narrative review

Sara Socorro Faria, Paulo César Fernandes Jr, Marcelo José Barbosa Silva, Vladmir C Lima, Wagner Fontes, Ruffo Freitas-Junior, Agda Karina Eterovic, Patrice Forget, Sara Socorro Faria, Paulo César Fernandes Jr, Marcelo José Barbosa Silva, Vladmir C Lima, Wagner Fontes, Ruffo Freitas-Junior, Agda Karina Eterovic, Patrice Forget

Abstract

Cellular-mediated inflammatory response, lymphocytes, neutrophils, and monocytes are increasingly being recognised as having an important role in tumorigenesis and carcinogenesis. In this context, studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) can be used as an independent prognostic factor in a variety of cancers. Particularly in breast cancer, several studies have shown that a high NLR is associated with shorter survival. Because the NLR can be easily determined from the full blood count, it could potentially provide a simple and inexpensive test cancer prognosis. This review addresses the possibilities and limitations of using the NLR as a clinical tool for risk stratification helpful for individual treatment of breast cancer patients. The potential underlying phenomena and some perspectives are discussed.

Keywords: breast cancer; inflammation; neutrophil-to-lymphocyte ratio; prognosis.

References

    1. Siegel R, Ma J, Zou Z, et al. Cancer statistics. Ca Cancer J Clin. 2014;64(1):9–29. doi: 10.3322/caac.21208.
    1. Saadatmand S, Bretveld R, Siesling S, et al. Influence of tumor stage at breast cancer detection on survival in modern times: population based study in 173797 patients. BMJ. 2015;351:h4901. doi: 10.1136/bmj.h4901.
    1. Guthrie GJ, Charles KA, Roxburgh CS, et al. The systemic inflammation-based neutrophil lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol. 2013;88(1):218–30. doi: 10.1016/j.critrevonc.2013.03.010.
    1. McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care. 2009;12:223–26. doi: 10.1097/MCO.0b013e32832a7902.
    1. Templeton AJ, Ace O, McNamara MG, et al. Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2014;23(7):1204–12. doi: 10.1158/1055-9965.EPI-14-0146.
    1. Denkert C, Loibl S, Noske A, et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2010;28(1):105–113. doi: 10.1200/JCO.2009.23.7370.
    1. Choi WJ, Cleghorn MC, Jiang H, et al. Preoperative neutrophil-to-lymphocyte ratio is a better prognostic serum biomarker than platelet-to-lymphocyte ratio in patients undergoing resection for nonmetastatic colorectal cancer. Ann Surg Oncol. 2015;22(Suppl 3):S603–13. doi: 10.1245/s10434-015-4571-7.
    1. Nishijima TF, Muss HB, Shachar SS, et al. Prognostic value of lymphocyte-to-monocyte ratio in patients with solid tumors: a systematic review and meta-analysis. Cancer Treat Rev. 2015;41(10):971–8. doi: 10.1016/j.ctrv.2015.10.003.
    1. Sanjay P, de Figueiredo RS, Leaver H, et al. Preoperative serum C-reactive protein levels and post-operative lymph node ratio are important predictors of survival after pancreatic duodenectomy for pancreatic ductal adenocarcinoma. JOP. 2012;13(2):199–204.
    1. Mallappa S, Sinha A, Gupta S, et al. Preoperative neutrophil to lymphocyte ratio > 5 is a prognostic factor for recurrent colorectal cancer. Colorectal Dis. 2013;15(3):323–328. doi: 10.1111/codi.12008.
    1. Cho H, Hur HW, Kim SW, et al. 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. doi: 10.1007/s00262-008-0516-3.
    1. Gondo T, Nakashima J, Ohno Y, et al. Prognostic value of neutrophiltolymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy. Urology. 2012;79(5):1085–91. doi: 10.1016/j.urology.2011.11.070.
    1. An X, Ding PR, Li YH, et al. Elevated neutrophil to lymphocyte ratio predicts survival in advanced pancreatic cancer. Biomarkers. 2010;15(6):516–22. doi: 10.3109/1354750X.2010.491557.
    1. Ohno Y, Nakashima J, Ohori M, et al. Clinical variables for predicting metastatic renal cell carcinoma patients who might not benefit from cytoreductive nephrectomy: neutrophil-to-lymphocyte ratio and performance status. Int J Clin Oncol. 2014;19(1):139–45. doi: 10.1007/s10147-012-0514-5.
    1. Forget P, Bentin C, Machiels JP, et al. Intraoperative use of ketorolac or diclofenac is associated with improved disease-free survival and overall survival in conservative breast cancer surgery. Br J Anaesth. 2014;113(1):82–7. doi: 10.1093/bja/aet464.
    1. Dirican A, Kucukzeybek BB, Alacacioglu A, et al. Do the derived neutrophil to lymphocyte ratio and the neutrophil to lymphocyte ratio predict prognosis in breast cancer? Int J Clin Oncol. 2014;18:18.
    1. Jie C, Qiwen D, Yuqin P, et al. Prognostic value of neutrophil-to-lymphocyte ratio in breast cancer. FEBS Open Bio. 2015;5:502–07. doi: 10.1016/j.fob.2015.05.003.
    1. Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. Arch Pathol Lab Med. 2014;138(2):241–56. doi: 10.5858/arpa.2013-0953-SA.
    1. Cimino-Mathews A, Foote J, Emens L. Immune targeting in breast cancer. Cancer Network. 2015;29:375–85.
    1. Galdiero MR, Bonavita E, Barajon I, et al. Tumor associated macrophages and neutrophils in cancer. Immunobiology. 2013;218(11):1402–10. doi: 10.1016/j.imbio.2013.06.003.
    1. Balkwill FR, Mantovani A. Cancer-related inflammation: common themes and therapeutic opportunities. Semin Cancer Biol. 2012;22:33–40. doi: 10.1016/j.semcancer.2011.12.005.
    1. Noh H, Eomm M, Han A. Usefulness of pretreatment neutrophil to lymphocyte ratio in predicting disease-specific survival in breast cancer patients. J Breast Cancer. 2013;16:55–9. doi: 10.4048/jbc.2013.16.1.55.
    1. Wculek SK, Malanchi I. Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature. 2015;528(7582):413–7. doi: 10.1038/nature16140.
    1. Coffelt SB, Kersten K, Doornebal CW, et al. IL17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature. 2015;522(7556):345–348. doi: 10.1038/nature14282.
    1. Jablonska J, Leschner S, Westphal K, et al. Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model. J Clin Investig. 2010;120:1151–64. doi: 10.1172/JCI37223.
    1. Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature. 2008;454(7203):436–44. doi: 10.1038/nature07205.
    1. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19(11):1423–37. doi: 10.1038/nm.3394.
    1. Cao J, Zhu X, Zhao X, et al. Coleman WB, editor. Neutrophil-to-lymphocyte ratio predicts PSA response and prognosis in prostate cancer: a systematic review and meta-analysis. PLoS One. 2016;11(7):e0158770. doi: 10.1371/journal.pone.0158770.
    1. Chen J, Deng Q, Pan Y, et al. Prognostic value of neutrophil-to-lymphocyte ratio in breast cancer. FEBS Open Bio. 2015;5:502–7. doi: 10.1016/j.fob.2015.05.003.
    1. Azab B, Bhatt VR, Phookan 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(1):217–24. doi: 10.1245/s10434-011-1814-0.
    1. Krenn-Pilko S, Langsenlehner U, Thurner EM, et al. The elevated preoperative platelet-to-lymphocyte ratio predicts poor prognosis in breast cancer patients. Br J Cancer. 2014;110:2524–30. doi: 10.1038/bjc.2014.163.
    1. Suppan C, Bjelic-Radisic V, La Garde M, et al. Neutrophil/lymphocyte ratio has no predictive or prognostic value in breast cancer patients undergoing preoperative systemic therapy. BMC Cancer. 2015;15:1027. doi: 10.1186/s12885-015-2005-3.
    1. Koh CH, Bhoo-Pathy N, Ng KL, et al. Utility of pretreatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer. Br J Cancer. 2015;113(1):150–8. doi: 10.1038/bjc.2015.183.
    1. Negrier S, Escudier B, Gomez F, et al. Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d’Immunotherapie. Ann Oncol. 2002;13:1460–8. doi: 10.1093/annonc/mdf257.
    1. Schmidt H, Suciu S, Punt CJA, et al. 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 biochemo therapy trial. J Clin Oncol. 2007;25:1562–9. doi: 10.1200/JCO.2006.09.0274.
    1. Proctor MJ, McMillan DC, Morrison DS, et al. A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer. Brit J of Cancer. 2012;107(4):695–9. doi: 10.1038/bjc.2012.292.
    1. Azab B, Shah N, Radbel J, et al. Pretreatment neutrophil/lymphocyte ratio is superior to platelet/lymphocyte ratio as a predictor of long-term mortality in breast cancer patients. Med Oncol. 2013;30(1):432. doi: 10.1007/s12032-012-0432-4.
    1. Ulas A, Avci N, Kos T, et al. Are neutrophil/lymphocyte ratio and platelet/lymphocyte ratio associated with prognosis in patients with HER2-positive early breast cancer receiving adjuvant trastuzumab? J BUON. 2015;20(3):714–22.
    1. Sato H, Tsubosa Y, Kawano T. Correlation between the pretherapeutic neutrophil to lymphocyte ratio and the pathologic response to neoadjuvant chemotherapy in patients with advanced esophageal cancer. World J Surg. 2012;36:617–22. doi: 10.1007/s00268-011-1411-1.
    1. Pistelli M, De Lisa M, Ballatore Z, et al. Pre-treatment neutrophil to lymphocyte ratio may be a useful tool in predicting survival in early triple negative breast cancer patients. BMC Cancer. 2015;15:195. doi: 10.1186/s12885-015-1204-2.
    1. Bozkurt O, Karaca H, Berk V, et al. Predicting the role of the pretreatment neutrophil to lymphocyte ratio in the survival of early triple-negative breast cancer patients. J BUON. 2015;20(6):1432–9.
    1. Wculek SK, Malanchi I. Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature. 2015;528:413–7. doi: 10.1038/nature16140.
    1. The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70. doi: 10.1038/nature11412.
    1. Malorni L, Shetty PB, Dc Angelis C, et al. Clinical and biologic features of triple-negative breast cancers in a large cohort of patients with long-term follow‑up. Breast Cancer Res Treat. 2012;136:795–804. doi: 10.1007/s10549-012-2315-y.
    1. Asano Y, Kashiwagi S, Onoda N, et al. Predictive value of neutrophil/lymphocyte ratio for efficacy of preoperative chemotherapy in triple-negative breast cancer. Ann Surg Oncol. 2015;28
    1. Jia W, Wu J, Jia H, et al. The peripheral blood neutrophil-to-lymphocyte ratio is superior to the lymphocyte-to-monocyte ratio for predicting the long-term survival of triple-negative breast cancer patients. PLoS One. 2015;10(11):e0143061. doi: 10.1371/journal.pone.0143061.
    1. Brown SD. Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival. Genome Res. 2014;24:743–50. doi: 10.1101/gr.165985.113.
    1. Galon J, Pagès F, Marincola FM, et al. Cancer classification using the immunoscore: a worldwide task force. J Transl Med. 2012;10:205. doi: 10.1186/1479-5876-10-205.
    1. M de Pedro S, Baeza MT, Escudero T, et al. Effect of COX-2 inhibitors and other non-steroidal inflammatory drugs on breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2015;149(2):525–36. doi: 10.1007/s10549-015-3267-9.
    1. Garcia-Albeniz X, Chan AT. Aspirin for the prevention of colorectal cancer. Best Pract Res Clingastroenterol. 2011;25:461–72. doi: 10.1016/j.bpg.2011.10.015.
    1. Forget P, Vandenhende J, Berliere M, et al. Do intraoperative analgesics influence breast cancer recurrence after mastectomy? A retrospective analysis. Anesth Analg. 2010;110(6):1630–5. doi: 10.1213/ANE.0b013e3181d2ad07.
    1. Choi JE, Villarreal J, Lasala J, et al. Perioperative neutrophil:lymphocyte ratio and postoperative NSAID use as predictors of survival after lung cancer surgery: a retrospective study. Cancer Med. 2015;4(6):825–33. doi: 10.1002/cam4.428.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren