Inflammation-Based Scores Increase the Prognostic Value of Circulating Tumor Cells in Primary Breast Cancer

Svetlana Miklikova, Gabriel Minarik, Tatiana Sedlackova, Jana Plava, Marina Cihova, Silvia Jurisova, Katarina Kalavska, Marian Karaba, Juraj Benca, Bozena Smolkova, Michal Mego, Svetlana Miklikova, Gabriel Minarik, Tatiana Sedlackova, Jana Plava, Marina Cihova, Silvia Jurisova, Katarina Kalavska, Marian Karaba, Juraj Benca, Bozena Smolkova, Michal Mego

Abstract

A correlation between circulating tumor cells (CTCs) and monocytes in metastatic breast cancer (BC), where CTCs and monocyte-to-lymphocyte ratio (MLR) were predictors of overall survival (OS), was recently shown. Herein, we aimed to assess the association between CTCs and the complete blood count (CBC)-derived inflammation-based scores in 284 primary BC patients. CTCs were determined in CD45-depleted peripheral blood mononuclear cells by real time-PCR. This method allowed us to detect a subset of CTCs with an epithelial-to-mesenchymal transition phenotype (CTC EMT), previously associated with inferior outcomes in primary BC. In the present study, CTC EMT positivity (hazard ratio (HR) = 2.4; 95% CI 1.20-4.66, p = 0.013) and elevated neutrophil-to-lymphocyte ratio (NLR) (HR = 2.20; 95% CI 1.07-4.55; p = 0.033) were associated with shorter progression-free survival (PFS) in primary BC patients. Multivariate analysis showed that CTC EMT-positive patients with NLR ≥ 3 had 8.6 times increased risk of disease recurrence (95% CI 2.35-31.48, p = 0.001) compared with CTC EMT-negative patients with NLR < 3. Similarly, disease recurrence was 13.14 times more likely in CTC EMT-positive patients with MLR ≥ 0.34 (95% CI 4.35-39.67, p < 0.001). Given its low methodological and financial demands, the CBC-derived inflammation-based score determination could, after broader validation, significantly improve the prognostication of BC patients.

Keywords: breast cancer; circulating tumor cells; monocyte-to-lymphocyte ratio; neutrophil-to-lymphocyte ratio; platelet-to-lymphocyte ratio; systemic immune-inflammation index.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier PFS estimates for CTC EMT. CTC EMT-positive patients had significantly shorter progression-free survival (PFS) than CTC EMT-negative patients (p = 0.010 by Log-rank test).
Figure 2
Figure 2
Kaplan–Meier PFS estimates for NLR (a) and MLR (b) status. PFS was significantly reduced in patients with NLR ≥ 3 compared to those with NLR < 3 (p = 0.029 by Log-rank test), while the difference was not significant for MLR (p = 0.109 by Log-rank test).
Figure 3
Figure 3
Kaplan–Meier PFS estimates for combinations of CTC EMT and NLR index. CTC EMT-positive patients with NLR ≥ 3 had shorter PFS compared to patients with any other combination of CTC EMT and NLR (p = 0.003 by Log-rank test).
Figure 4
Figure 4
Kaplan–Meier PFS estimates for combinations of CTC EMT and MLR index. CTC EMT-positive patients with MLR ≥ 0.34 had shorter PFS compared to patients with all other combinations of CTC EMT and MLR (p < 0.001 by Log-rank test).

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