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

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.

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

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

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

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).