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. 2018 May 17:11:2901-2910.
doi: 10.2147/OTT.S160911. eCollection 2018.

High neutrophil to lymphocyte ratio and decreased CD69+NK cells represent a phenotype of high risk in early-stage breast cancer patients

Pablo Mandó #  1 , Manglio Rizzo #  2 , María Paula Roberti  1 , Estefanía Paula Juliá  1 , María Betina Pampena  1 , Constanza Pérez de la Puente  2 , Carlos Martín Loza  2 , Carolina Ponce  2 , Jorge Nadal  2 , Federico Andres Coló  2 , José Mordoh  1   2   3 , Estrella Mariel Levy  1
Affiliations

High neutrophil to lymphocyte ratio and decreased CD69+NK cells represent a phenotype of high risk in early-stage breast cancer patients

Pablo Mandó et al. Onco Targets Ther. .

Abstract

Purpose: Breast cancer (BC) is a highly heterogeneous disease presenting a broad range of clinical and molecular characteristics. In the past years, a growing body of evidence demonstrated that immune response plays a significant role in cancer outcome. However, immune prognostic markers are not completely validated in clinical practice in BC patients.

Materials and methods: With the aim to characterize immune features, several parameters were analyzed in peripheral blood at diagnosis of 85 nonmetastatic BC patients between April 2011 and July 2014.

Results: With a median follow-up of 38.6 months, peripheral blood analysis of BC patients (stages I, II, and III) showed that total lymphocyte and T lymphocyte counts were augmented in nonrelapsed patients. Also, a higher neutrophil-to-lymphocytes ratio was associated with prolonged disease-free survival. Natural killer cell receptor analysis revealed that early activation receptor CD69 was associated with a better outcome.

Conclusion: This preliminary evidence is in accordance with the concept of immune surveillance. We suggest an "immune phenotype" that provides relevant prognostic information in early-stage BC patients and which could be useful in the decision-making process.

Keywords: breast neoplasm; lymphocytes; neutrophil-to-lymphocyte ratio; prognostic factors.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Total lymphocytes and T lymphocytes differences in R and NR patients. Notes: Bars show median PB cells absolute number (upper panel) and percentage (lower panel), from R (gray) and NR (white) patients. Wilcoxon rank sum test was performed. Significant p-values are shown in the graph. Abbreviations: NR, nonrelapsed; PB, peripheral blood; R, relapsed.
Figure 2
Figure 2
NLR association with DFS. Notes: NLR variable was dichotomized as high (≥2) or low (<2). Patients with a NLR ≥2 presented a significantly lower DFS (5-year DFS: 100% vs 69.55%, p=0.048) and a tendency toward higher recurrence risk (p=0.058). Significant p-value is shown in the graph. Low NLR is depicted with a red line and high NLR with a black line. Abbreviations: DFS, disease-free survival; NLR, neutrophil to lymphocyte ratio.
Figure 3
Figure 3
NK cells analysis in R and NR patients. Notes: (A) Bars show median NK cells and NKT cells absolute number (up) and percentage (down) from R (gray) and NR (white) patients. There is no difference between R and NR patients. (B) Patients were classified as CD69 “high” or “low” expression in relation to population median (1.7%). NK cells from R patients expressed lower CD69 than NR (p=0.047). This association was also reflected in DFS (5-year DFS high 87.70% vs low 63.75%, p=0.045). χ2 and log rank test were performed, respectively. Significant p-value is shown in the graph. In Kaplan–Meier curve, CD69 high was depicted with a red line and CD69 low with a black one. Abbreviations: DFS, disease-free survival; NK, natural killer; NR, nonrelapsed; R, relapsed.
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