Abstract

PurposeThe aim of this study was to investigate the prognostic impact of two systemic inflammatory markers, the neutrophil-to-lymphocyte ratio (NLR) and the monocyte-to-lymphocyte ratio (MLR), and their possible predictive role regarding the efficacy of adjuvant trastuzumab, in 209 early breast cancer cases, 107 of which were HER2-positive.MethodsBaseline NLR and MLR values were divided into two groups, high and low, according to cut-off-points determined from the ROC curve (2.2 for NLR and 0.22 for MLR). Cox’s model was utilized for survival analyses.ResultsHigh NLR and MLR correlated with poor overall survival (OS) and breast cancer specific survival (BCSS) among all the patients (p ≤ 0.030). Among the HER2+ patients whose adjuvant treatment did not include trastuzumab (n = 64), the survival rates were remarkably lower in patients with a high NLR as compared to those with low; 31% vs. 71% for OS and 42% vs. 74% for BCSS (p ≤ 0.014). Similarly, high MLR correlated with poor survival among these patients (p ≤ 0.020). On the contrary, among the patients who had received adjuvant trastuzumab (n = 43), NLR or MLR did not correlate with survival. Furthermore, trastuzumab was beneficial for the HER2+ patients with high NLR/MLR, while the survival of the HER2+ patients with low NLR/MLR was good irrespective if they received adjuvant trastuzumab.ConclusionsOur results suggest that trastuzumab modulates the systemic inflammatory conditions and overcomes the poor prognostic impact of high NLR/MLR. This finding may also provide a rationale for combining trastuzumab with immuno-oncological treatments in HER2+ breast cancer.

Highlights

  • Systemic inflammatory state of the host and the inflammatory response in the tumor microenvironment have a remarkable impact on cancer progression [1, 2]

  • The optimal cut-off-points calculated with the receiver operating characteristic (ROC) curve were 2.2 for neutrophil-to-lymphocyte ratio (NLR) (AUC 0.624, 95% CI 0.54–0.71, p = 0.006) and 0.22 for monocyte-tolymphocyte ratio (MLR) (AUC 0.597, 95% CI 0.51–0.68, p = 0.031)

  • We found that the outcome of the human epidermal growth factor receptor 2 (HER2)+ breast cancer (BC) patients with a high NLR or MLR was poor if their adjuvant treatment did not include trastuzumab

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Summary

Introduction

Systemic inflammatory state of the host and the inflammatory response in the tumor microenvironment have a remarkable impact on cancer progression [1, 2]. Breast Cancer Research and Treatment (2021) 185:63–72 neutrophil-to-lymphocyte ratio (NLR) and monocyte-tolymphocyte ratio (MLR) can be considered as indicators of the host’s systemic inflammatory state [7], i.e., high NLR and MLR may reflect poor anti-tumor immunity. Several studies have investigated the prognostic role of NLR in breast cancer (BC) [7]. Some publications suggest that a high MLR associates with a poor outcome in BC [7, 10] but there are studies reporting no correlation between MLR and BC outcome [7, 11]

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