No 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.

Aim: Different types of chronic medication may affect breast cancer prognosis. Circulating tumor cells (CTCs) play an important role in cancer metastasis formation. There is no evidence of how chronic medication affects CTCs and breast cancer prognosis. The aim of this study was to evaluate association between chronic medication and CTCs in patients with primary breast cancer. Methods: This study involved 414 patients with stage I-III primary breast cancer. Chronic drug history was collected from patients' medical records and included all drugs that were prescribed for patients over at least the last 6 months prior to CTCs evaluation. CTCs were detected using a quantitative real-time polymerase chain reaction (qRT-PCR)-based method at the time of breast surgery. Results: There was no association between CTCs, including their different subpopulations and chronic medication. Chronic medication using angiotensin-converting-enzyme inhibitors (ACEi), metformin, and insulin were associated with inferior disease-free survival (HR = 0.49, 95%CI 0.26-0.94, P = 0.007 for ACEi; HR = 0.27, 95%CI 0.08-0.91, P < 0.001 for metformin; and HR = 0.12, 95%CI 0.01-2.91, P < 0.001 for insulin) and this was most pronounced in patients with epithelial to mesenchymal transition (CTC_EMT) phenotype. In multivariate analysis, chronic administration of metformin and/or insulin was an independent predictor of inferior outcome. Conclusion: Our findings show that there was no association between chronically used medication and CTCs in primary breast cancer patients. However, administration of ACEi, metformin, and/or insulin could negatively affect prognosis of patients with CTC_EMT.

Even though the blood coagulation pathway may be activated in more aggressive disease related to an elevated CTC count, in this study, we did not find any association between CTCs and plasma concentrations of tPA.