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Tumor Biology

, Volume 37, Issue 7, pp 9037–9043 | Cite as

Pretreatment lymphocyte to monocyte ratio as a predictor of prognosis in patients with early-stage triple-negative breast cancer

  • Juanjuan He
  • Pengwei Lv
  • Xue Yang
  • Yanli Chen
  • Chao Liu
  • Xinguang Qiu
Original Article

Abstract

Recent studies have shown that the lymphocyte to monocyte ratio (LMR) is a useful prognostic factor in various cancers. The purpose of the current study was to investigate the association between pretreatment LMR, disease-free survival (DFS), and overall survival (OS) in patients with early-stage (I to III) triple-negative breast cancer (TNBC). Pretreatment LMR with corresponding clinical features from 230 TNBC patients was noted. A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimal cutoff values for LMR, lymphocyte, and monocyte counts. The difference between variables was calculated using chi-square tests. The Kaplan–Meier method and univariate and multivariate Cox regression models were applied to assess OS and DFS. Based on the ROC analysis, the optimal cutoff point for LMR was 4.7. Associations between high LMR (≥4.7) and significantly small tumor size (P = 0.005) and TNM stage (P = 0.013) were found, although there was no significant association for other clinical pathological factors. In the multivariate analysis, LMR was a significant predictive factor for both OS (hazard ratio [HR] = 0.42; 95 % confidence interval [CI], 0.19–0.95; P < 0.001) and DFS (HR = 0.40; 95 % CI, 0.20–0.79; P < 0.001). In addition, the predictive values of the OS and DFS were also observed for absolute counts of lymphocytes (P < 0.001) and monocytes (P < 0.001). Our study suggests that pretreatment LMR may be a predictive factor for long-term survival in patients with early-stage TNBC.

Keywords

Triple-negative breast cancer Lymphocyte to monocyte ratio Disease-free survival Overall survival 

Notes

Compliance with ethical standards

Conflicts of interest

None.

Supplementary material

13277_2016_4793_Fig4_ESM.gif (99 kb)
Fig. S1

Distribution of the baseline LMR (a), ALC (b) and AMC (c) in the peripheral blood of 230 patients with triple-negative breast cancer. Abbreviations: ALC, Absolute lymphocyte count; AMC, Absolute monocyte count; LMR, Lymphocyte-to-monocyte ratio (GIF 98 kb)

13277_2016_4793_MOESM1_ESM.tif (3.2 mb)
High Resolution Image (TIF 3277 kb)
13277_2016_4793_Fig5_ESM.gif (35 kb)
Fig. S2

ROC curves analyses for disease-free survival prediction were plotted to verify the optimal cut-off points for LMR (a), ALC (b), and AMC (c) (GIF 35 kb)

13277_2016_4793_MOESM2_ESM.tif (804 kb)
High Resolution Image (TIF 803 kb)
13277_2016_4793_Fig6_ESM.gif (58 kb)
Fig. S3

Kaplan–Meier survival analysis of baseline ALC and AMC in patients with triple-negative breast cancer. a, OS curve for ALC; b, DFS curve for ALC; c, OS curve for AMC; d, DFS curve for AMC. Abbreviations: ALC, absolute lymphocyte count; AMC, absolute monocyte count (GIF 58 kb)

13277_2016_4793_MOESM3_ESM.tif (2.2 mb)
High Resolution Image (TIF 2269 kb)
13277_2016_4793_MOESM4_ESM.doc (36 kb)
ESM 4 (DOC 36 kb)

References

  1. 1.
    Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363(20):1938–48.CrossRefPubMedGoogle Scholar
  2. 2.
    Mancini P, Angeloni A, Risi E, Orsi E, Mezi S. Standard of care and promising new agents for triple negative metastatic breast cancer. Cancers (Basel). 2014;6(4):2187–223.CrossRefGoogle Scholar
  3. 3.
    Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750–67.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    van ‘t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530–6.CrossRefGoogle Scholar
  5. 5.
    Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 2014;15(11):e493–503.CrossRefPubMedGoogle Scholar
  6. 6.
    Matsumoto H, Koo SL, Dent R, Tan PH, Iqbal J. Role of inflammatory infiltrates in triple negative breast cancer. J Clin Pathol. 2015;68(7):506–10.CrossRefPubMedGoogle Scholar
  7. 7.
    Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.CrossRefPubMedGoogle Scholar
  8. 8.
    Halazun KJ, Hardy MA, Rana AA, Woodland DC, Luyten EJ, Mahadev S, et al. Negative impact of neutrophil-lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma. Ann Surg. 2009;250(1):141–51.CrossRefPubMedGoogle Scholar
  9. 9.
    De Giorgi U, Mego M, Scarpi E, Giuliano M, Giordano A, Reuben JM, et al. Relationship between lymphocytopenia and circulating tumor cells as prognostic factors for overall survival in metastatic breast cancer. Clin Breast Cancer. 2012;12(4):264–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Zhang Y, Cheng S, Zhang M, Zhen L, Pang D, Zhang Q, et al. High-infiltration of tumor-associated macrophages predicts unfavorable clinical outcome for node-negative breast cancer. PLoS One. 2013;8(9):e76147.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Jiang R, Cai XY, Yang ZH, Yan Y, Zou X, Guo L, et al. Elevated peripheral blood lymphocyte-to-monocyte ratio predicts a favorable prognosis in the patients with metastatic nasopharyngeal carcinoma. Chin J Cancer. 2015;34(1):23.CrossRefPubMedCentralGoogle Scholar
  12. 12.
    Yuan ZY, Luo RZ, Peng RJ, Wang SS, Xue C. High infiltration of tumor-associated macrophages in triple-negative breast cancer is associated with a higher risk of distant metastasis. Oncol Targets Ther. 2014;7:1475–80.CrossRefGoogle Scholar
  13. 13.
    Li ZM, Huang JJ, Xia Y, Sun J, Huang Y, Wang Y, et al. Blood lymphocyte-to-monocyte ratio identifies high-risk patients in diffuse large B-cell lymphoma treated with R-CHOP. PLoS One. 2012;7(7):e41658.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Porrata LF, Inwards DJ, Ansell SM, Micallef IN, Johnston PB, Hogan WJ, et al. Infused autograft lymphocyte to monocyte ratio predicts survival in classical Hodgkin lymphoma. J Blood Med. 2015;6:45–53.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Zhou X, Du Y, Xu J, Huang Z, Qiu T, Wang X, et al. The preoperative lymphocyte to monocyte ratio predicts clinical outcomes in patients with stage II/III gastric cancer. Tumour Biol. 2014;35(11):11659–66.CrossRefPubMedGoogle Scholar
  16. 16.
    Ying HQ, Deng QW, He BS, Pan YQ, Wang F, Sun HL, et al. The prognostic value of preoperative NLR, d-NLR, PLR and LMR for predicting clinical outcome in surgical colorectal cancer patients. Med Oncol. 2014;31(12):305.CrossRefPubMedGoogle Scholar
  17. 17.
    Lin GN, Peng JW, Liu DY, Xiao JJ, Chen YQ, Chen XQ. Increased lymphocyte to monocyte ratio is associated with better prognosis in patients with newly diagnosed metastatic nasopharyngeal carcinoma receiving chemotherapy. Tumour Biol. 2014;35(11):10849–54.CrossRefPubMedGoogle Scholar
  18. 18.
    Chen YM, Lai CH, Chang HC, Chao TY, Tseng CC, Fang WF, et al. Baseline and trend of lymphocyte-to-monocyte ratio as prognostic factors in epidermal growth factor receptor mutant non-small cell lung cancer patients treated with first-line epidermal growth factor receptor tyrosine kinase inhibitors. PLoS One. 2015;10(8):e0136252.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Ni XJ, Zhang XL, Ou-Yang QW, Qian GW, Wang L, Chen S, et al. An elevated peripheral blood lymphocyte-to-monocyte ratio predicts favorable response and prognosis in locally advanced breast cancer following neoadjuvant chemotherapy. PLoS One. 2014;9(11):e111886.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Rosen PPOH. Tumors of the mammary gland. Washington, DC: Armed Forces Institute of Pathology; 1993. p. 332.Google Scholar
  21. 21.
    Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. C. W. Elston & I. O. Ellis. Histopathology 1991; 19; 403–410. Histopathology 2002;41(3A):151–2, discussion 152–3.Google Scholar
  22. 22.
    Mroczko B, Groblewska M, Wereszczynska-Siemiatkowska U, Okulczyk B, Kedra B, Laszewicz W, et al. Serum macrophage-colony stimulating factor levels in colorectal cancer patients correlate with lymph node metastasis and poor prognosis. Clin Chim Acta. 2007;380(1–2):208–12.CrossRefPubMedGoogle Scholar
  23. 23.
    Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21(2):137–48.CrossRefPubMedGoogle Scholar
  24. 24.
    Bastid J, Bonnefoy N, Eliaou JF, Bensussan A. Lymphocyte-derived interleukin-17A adds another brick in the wall of inflammation-induced breast carcinogenesis. Oncoimmunology. 2014;3:e28273.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Sarraf KM, Belcher E, Raevsky E, Nicholson AG, Goldstraw P, Lim E. Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer. J Thorac Cardiovasc Surg. 2009;137(2):425–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Adams S, Goldstein LJ, Sparano JA, Demaria S, Badve SS. Tumor infiltrating lymphocytes (TILs) improve prognosis in patients with triple negative breast cancer (TNBC). Oncoimmunology. 2015;4(9):e985930.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Youn JI, Collazo M, Shalova IN, Biswas SK, Gabrilovich DI. Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice. J Leukoc Biol. 2012;91(1):167–81.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007;13(9):1050–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Nazir T, Islam A, Omer MO, Mustafa M. Lymphocytopenia; induced by vinorelbine, doxorubicin and cisplatin in human cancer patients. Breast Dis. 2015;35(1):1–4.CrossRefPubMedGoogle Scholar
  30. 30.
    Saroha S, Uzzo RG, Plimack ER, Ruth K, Al-Saleem T. Lymphopenia is an independent predictor of inferior outcome in clear cell renal carcinoma. J Urol. 2013;189(2):454–61.CrossRefPubMedGoogle Scholar
  31. 31.
    Stotz M, Pichler M, Absenger G, Szkandera J, Arminger F, Schaberl-Moser R, et al. The preoperative lymphocyte to monocyte ratio predicts clinical outcome in patients with stage III colon cancer. Br J Cancer. 2014;110(2):435–40.CrossRefPubMedGoogle Scholar
  32. 32.
    He JR, Shen GP, Ren ZF, Qin H, Cui C, Zhang Y, et al. Pretreatment levels of peripheral neutrophils and lymphocytes as independent prognostic factors in patients with nasopharyngeal carcinoma. Head Neck. 2012;34(12):1769–76.CrossRefPubMedGoogle Scholar
  33. 33.
    Evani SJ, Prabhu RG, Gnanaruban V, Finol EA, Ramasubramanian AK. Monocytes mediate metastatic breast tumor cell adhesion to endothelium under flow. FASEB J. 2013;27(8):3017–29.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Watari K, Shibata T, Kawahara A, Sata K, Nabeshima H, Shinoda A, et al. Tumor-derived interleukin-1 promotes lymphangiogenesis and lymph node metastasis through M2-type macrophages. PLoS One. 2014;9(6):e99568.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Yang C, He L, He P, Liu Y, Wang W, He Y, et al. Increased drug resistance in breast cancer by tumor-associated macrophages through IL-10/STAT3/bcl-2 signaling pathway. Med Oncol. 2015;32(2):352.CrossRefPubMedGoogle Scholar
  36. 36.
    Go SI, Kim RB, Song HN, Kang MH, Lee US, Choi HJ, et al. Prognostic significance of the lymphocyte-to-monocyte ratio in patients with small cell lung cancer. Med Oncol. 2014;31(12):323.CrossRefPubMedGoogle Scholar
  37. 37.
    Remark R, Becker C, Gomez JE, Damotte D, Dieu-Nosjean MC, Sautes-Fridman C, et al. The non-small cell lung cancer immune contexture. A major determinant of tumor characteristics and patient outcome. Am J Respir Crit Care Med. 2015;191(4):377–90.CrossRefPubMedGoogle Scholar
  38. 38.
    Alkhouri N, Morris-Stiff G, Campbell C, Lopez R, Tamimi TA, Yerian L, et al. Neutrophil to lymphocyte ratio: a new marker for predicting steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease. Liver Int. 2012;32(2):297–302.CrossRefPubMedGoogle Scholar
  39. 39.
    Buyukkaya E, Karakas MF, Karakas E, Akcay AB, Tanboga IH, Kurt M, et al. Correlation of neutrophil to lymphocyte ratio with the presence and severity of metabolic syndrome. Clin Appl Thromb Hemost. 2014;20(2):159–63.CrossRefPubMedGoogle Scholar
  40. 40.
    Azab B, Bhatt VR, Phookan J, Murukutla S, Kohn N, Terjanian T, 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.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Juanjuan He
    • 1
  • Pengwei Lv
    • 1
  • Xue Yang
    • 1
  • Yanli Chen
    • 1
  • Chao Liu
    • 1
  • Xinguang Qiu
    • 2
  1. 1.Department of Breast Surgery, The First Affiliated HospitalZhengzhou UniversityZhengzhouChina
  2. 2.Department of Thyroid Surgery, The First Affiliated HospitalZhengzhou UniversityZhengzhouPeople’s Republic of China

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