Prognostic significance of pretreatment inflammatory biomarkers in non-metastatic breast cancer

Abstract

Background: Recently, peripheral blood inflammatory biomarkers such as neutrophil-lymphocyte ratio (NLR) have been identified for their prognostic role in many types of cancers. Elevated NLR was associated with poor prognosis & increased mortality rates. This study assessed the predictive value of pretreatment NLR in non-metastatic breast cancer.
Objective: To assess the role of pretreatment NLR in non-metastatic breast cancer and their effect on prognosis in terms of 5 years disease-free survival and overall survival.
Methods: This retrospective cross-sectional study was conducted in Suez Canal University Hospitals in Ismailia, Egypt. 105 patients with pathologically proven breast cancer were recruited from January 2015 to December 2016. Patients & tumor characteristics were collected from medical records. Five-year overall survival & disease-free survival were analyzed.
Results: Mean patients’ ages were 47.82 ± 11.65. The age ranges were between 25 & 78 years. There was no statistical significance between patients with low & high pretreatment NLR in terms of patients’ characteristics & tumor variables. With the ROC curve, the cut-off points for NLR were 1.65 & 1.55 for DFS and OS, respectively. In terms of patients’ DFS & OS, no statistically significant difference was found between non-metastatic breast cancer patients with low & high NLR (p_log-rank =.357 and.236, respectively). No statistically significant difference was found between patients with low & high pretreatment NLR in the period of five years OS & DFS.
Conclusions: Pretreatment NLR is an inflammatory biomarker that might affect patient prognosis and survival. Further research is required to confirm the prognostic significance.

Keywords

NLR / Inflammatory biomarker / Prognosis / Breast cancer

References

[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. Cancer J Clin. 2016; 66(1): 7-30. PMid: 25559415. https://doi.org/10.3322/caac.21254

[2] Runowicz CD, Leach CR, Henry NL, et al. Society/American So- ciety of Clinical Oncology Breast Cancer Survivorship Care Guide- line. Cancer J Clin. 2016; 66(1): 43-73. PMid: 26641959. https://doi.org/10.3322/caac.21319

[3] Ibrahim AS, Khaled HM, Mikhail NN, et al. Cancer incidence in Egypt: Results of the national population-based cancer registry program. J Cancer Epidemiol. 2014; 437971. PMid: 25328522. https://doi.org/10.1155/2014/437971

[4] International Cancer Control Partnership: WHO Cancer Country Profiles 2020.March 9, 2020. [Accessed January 19, 2021]. Avail-able from: https://www.iccp-portal.org/news/who-cancer-country-profiles-2020

[5] Schlichting JA, Soliman AS, Schairer C, et al. Breast cancer by age at diagnosis in the Gharbiah, Egypt, population-based registry compared to the United States Surveillance, Epidemiology, and End Results Program, 2004-2008. BioMed Res Int. 2015; 381574. PMid: 26495294. https://doi.org/10.1155/2015/381574

[6] Elghazaly H, Aref TA, Anderson BO, et al. The first BGICC con- sensus and recommendations for breast cancer awareness, early de- tection, and risk reduction in low- and middle-income countries and the MENA region. Int J Cancer. February 9, 2021. PMid: 33559295. https://doi.org/10.1002/ijc.33506

[7] Ethier JL, Desautels D, Templeton A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: a systematic re- view and meta-analysis. Breast Cancer Res. 2017; 19(1): 2. PMid: 28057046. https://doi.org/10.1186/s13058-016-0794-1

[8] Hanahan D, Weinberg RA. Hallmarks of cancer: the next gen- eration. Cell. 2011; 144(5): 646-674. PMid: 21376230. https://doi.org/10.1016/j.cell.2011.02.013

[9] Fridman WH, Zitvogel L, Sautes-Fridman C, et al. The immune con- texture in cancer prognosis and treatment. Nat Rev Clinoncol. 2017; 14(12): 717-734. PMid: 28741618. https://doi.org/10.1038/nrclinonc.2017.101

[10] Coussens LM, Zitvogel L, Palucka AK, et al. Neutralizing tumor- promoting chronic inflammation: a magic bullet? Science. 203; 339: 286-91. PMid: 23329041. https://doi.org/10.1126/science.1232227

[11] Soysal SD, Tzankov A, Muenst SE, et al. Role of the Tumor Microen- vironment in Breast Cancer. Pathobiology. 2015; 82: 142-152. PMid: 26330355. https://doi.org/10.1159/000430499

[12] Ethier JL, Desautels D, Templeton, et al. Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: a systematic review and meta-analysis. Breast Cancer Res. 2017; 19: 2. PMid: 28057046. https://doi.org/10.1186/s13058-016-0794-1

[13] Zhang M, Huang XZ, Song YX, et al. High platelet-to-lymphocyte ratio predicts poor prognosis and clinicopathological characteristics in patients with breast cancer: a meta-analysis. Biomed Res Int. 2017; 2017: 9503025. PMid: 29082257. https://doi.org/10.1155/2017/9503025

[14] Wei B, Yao M, Xing C, et al. The neutrophil-lymphocyte ratio is associated with breast cancer prognosis: an updated systematic re- view and meta-analysis. Onco Targets Ther. 2016; 9: 5567-75. PMid: 27660475. https://doi.org/10.2147/OTT.S108419

[15] Templeton AJ, McNamara MG, Seruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J. Natl. Cancer. Inst. 2014; 106: 124. https://doi.org/10.1093/jnci/dju124

[16] Dolan RD, Laird BJA, Horgan PG, et al. The prognostic value of the systemic inflammatory response in randomised clinical trials in cancer: A systematic review. Crit. Rev. Oncol. Hematol. 2018; 132: 130-137. PMid: 30447918. https://doi.org/10.1016/j.critrevonc.2018.09.016

[17] Koh CH, Bhoo-Pathy N, Ng KL, et al. Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prog- nostic factors in breast cancer. Br. J. Cancer. 2015; 113: 150-158. PMid: 26022929. https://doi.org/10.1038/bjc.2015.183

[18] Orditura M, Galizia G, Diana A, et al. Neutrophil to lympho- cyte ratio (NLR) for prediction of distant metastasis-free survival (DMFS) in early breast cancer: a propensity score-matched anal- ysis. ESMO Open. 2016; 1: e000038. PMid: 27843594. https://doi.org/10.1136/esmoopen-2016-000038

[19] Azab B, Shah N, Radbel J, et al. Pretreatment neutrophil/lymphocyte ratio is superior to the platelet/lymphocyte ratio as a predictor of long- term mortality in breast cancer patients. Med. Oncol. 2013; 30: 432. PMid: 23283648. https://doi.org/10.1007/s12032-012-0432-4

[20] Charan J, Biswas T. How to calculate sample size for different study designs in medical research? Indian Journal of Psycholog- ical Medicine. 2013; 35(2): 121-126. PMid: 24049221. https://doi.org/10.4103/0253-7176.116232

[21] Ramos-Esquivel A, Rodriguez-Porras L, Porras J. Neutrophil- lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in non-metastatic breast cancer patients from a Hispanic popula- tion. Breast Disease. 2017; 37(1): 1-6. PMid: 28035906. https://doi.org/10.3233/BD-160251

[22] Cuello-López J, Fidalgo-Zapata A, Lopez-Agudelo L, et al. Platelet- To-lymphocyte ratio as a predictive factor of complete pathologic response to neoadjuvant chemotherapy in breast cancer. PLoS ONE. 2018; 13(11): 1-12. PMid: 30427884. https://doi.org/10.1371/journal.pone.0207224

[23] Xu J, Ni C, Ma C, et al. Association of the neutrophil/lymphocyte ratio and platelet/lymphocyte ratio with ER and PR in breast cancer patients and their changes after neoadjuvant chemotherapy. Clinical and Translational Oncology. 2017; 19(8): 989-996. PMid: 28247194. https://doi.org/10.1007/s12094-017-1630-5

[24] Xue LB, Liu YH, Zhang B, et al. Prognostic role of high neutrophil- to-lymphocyte ratio in breast cancer patients receiving neoadjuvant chemotherapy Meta-analysis. Medicine (United States). 2019; 98(1): E13842. PMid: 30608401. https://doi.org/10.1097/MD.0000000000013842

[25] Elyasinia F, Keramati MR, Ahmadi F, et al. Neutrophil-lymphocyte ratio in different stages of breast cancer. Acta Medica Iranica. 2017; 55(4): 228-232.

[26] Hong J, Mao Y, Chen X, et al. Elevated preoperative neutrophil- to-lymphocyte ratio predicts poor disease-free survival in Chinese women with breast cancer. Tumor Biology. 2016; 37(3): 4135-4142. PMid: 26490984. https://doi.org/10.1007/s13277-015-4233-1

[27] Cihan, Benderli Y, Alaettin, et al. Lack of prognostic value of blood parameters in patients receiving adjuvant radiotherapy for breast cancer. Asian Pacific Journal of Cancer Prevention. 2014; 15(10): 4225-4231. PMid: 24935375. https://doi.org/10.7314/APJCP.2014.15.10.4225

[28] Losada B, Guerra J.A, Malon D, et al. Pretreatment neu- trophil/lymphocyte, platelet/lymphocyte, lymphocyte/monocyte, and neutrophil/monocyte ratios and outcome in elderly breast cancer pa- tients. Clinical and Translational Oncology. 2019; 21(7): 855-863. PMid: 30506134. https://doi.org/10.1007/s12094-018-1999-9

[29] Graziano V, Grassadonia A, Iezzi L, et al. A Combination of periph- eral neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio is predictive of pathological complete response after neoadju- vant chemotherapy in breast cancer patients. Breast. 2019; 44: 33-38. PMid: 30611095. https://doi.org/10.1016/j.breast.2018.12.014