Prognostic Role of Platelets-to-Lymphocytes Ratio and Neutrophils-to-Lymphocytes Ratio in Breast Cancer Patients

Abstract

Breast cancer (BC) is the most common cancer in women. Several prognostic and predictive factors are usefully considered in clinical practice, but ongoing efforts are made by the scientific community to identify new biomarkers for prognostic models’ improvement and better tailoring of therapeutic choice. Factors associated with inflammation, which is a hallmark of cancer, represent an important object of study. Among these factors, Neutrophils to lymphocytes ratio (NLR) and Platelets to lymphocytes ratio (PLR) are the most analyzed and are associated with prognosis in many solid tumors. The aim of this study is to verify the prognostic role of NLR and PLR in patients affected by localized BC who underwent radiotherapy (RT). Between December 2007 and June 2012, 370 consecutive BC patients treated with adjuvant RT were analyzed. PLR and NLR were calculated as the absolute platelet count divided by the absolute lymphocyte count, and absolute neutrophil count divided by absolute lymphocyte count in a blood sample obtained soon before the start of the RT, respectively. Using receiver operating characteristic analysis PLR and NLR were dichotomized and the cut-off values were 180 (namely, h-PLR≥180, l-PLR<180) and 3.17 (namely, h-NLR≥3.17, l-NLR<3.17), respectively. The end points of the study were local control (LC), disease free survival (DFS), overall survival (OS) and distant metastasis free survival (DMFS). The relationship among NLR, PLR and other clinico-pathological features was studied by chi-square. The end points were calculated using the Kaplan-Meier method and compared by the log-rank test. Multivariable analysis was performed using Logistic Regression. At a median follow-up time of 77 months (range 5-129), 345 patients were alive. Eighteen patients died for disease progression, while 7 deaths were non-cancer related. There were 58 (15.7%) relapses of disease. Actuarial 5-year DFS and OS in h-NLR vs l-NLR were 62% vs 81% (p<0.001) and 85% vs 92% (p=0.010) respectively; similar result was found for PLR (68% vs 82%, p=0.002; 87% vs 93%, p=0.002). Both ratios resulted significantly associated with DMFS (PLR p=0.007, NLR p=0.002), while it was not observed for LC (PLR p= 0.2, NLR p=0.7). In logistic regression that included high Ki67, stage, NLR, PLR, age and chemotherapy (the last two only for DFS and DMFS), NLR was identified as an independent prognostic factor of poor outcome for OS, DFS and DMFS (p<0.05). Multivariate analysis also showed that advanced stage negatively affected DFS and DMFS (p<0.05). Finally, X2- test revealed a significant correlation between NLR and Ki67, Her2 overexpression, stage, and chemotherapy. NLR is a low-cost, reproducible marker available in all patients, its high value is associated with poor prognosis in BC, and it could be used to improve the management of these patients.