Abstract P2-02-04: In early breast cancer, the ratios of neutrophils, monocyctes and platelets to lymphocytes significantly correlate with the presence of subsets of circulating tumor cells in blood and disseminated tumor cells in the bone marrow
Authors: Kasimir-Bauer Sabine , Karaaslan Ebru , Hars Olaf , Bittner Ann-Kathrin , Hoffmann Oliver , Kimmig Rainer 
Published: March 2022

Abstract
Background: Circulating tumor cells (CTCs) are the precursors of metastasis and while travelling through the peripheral blood, they crosstalk with different types of blood cells before they finally reach distant organs to settle down as disseminated tumor cells (DTCs). Proinflammatory markers include the neutrophil lymphocyte ratio (NLR), the platelet lymphocyte ratio (PLR) as well as the monocyte lymphocyte ratio (MLR) and the presence of tumor cells as well as specific proinflammatory markers are two independent predictors of worse outcome in breast cancer (BC). However, little is known about the correlation between NLR, PLR, MLR and subsets of CTCs as well as DTCs in early, non-metastatic BC. Here we evaluated the correlation of NLR, PLR, MLR and the presence of epithelial CTCs (eCTCs), CTCs in epithelial mesenchymal transition (EMT-CTCs) as well as DTCs to better identify patients at risk, to monitor treatment reponse and probably adjust therapeutic options. Methods: The counts of peripheral neutrophils, lymphocytes, monocytes and platelets to determine NLR, PLR and MLR as well as clinicopathological data during diagnosis were retrospectively recorded for 171 patients (pts) diagnosed with BC from July 2006 to December 2012, before the start of therapy. NLR, PLR and MLR were calculated from peripheral blood cell counts and their optimal cutoff levels were determined by the 75% percentile resulting in the following values: NLR: 3.13, MLR: 0.39 and PLR: 222.3, respectively. 170/171 pts were analyzed for DTCs by immunocytochemistry using the pan-cytokeratin antibodyA45-B/B3 (Clodronate intake was recommended in case of DTC-positivity). CTCs were determined in 155/171 pts applying positive immunomagnetic selection using the AdnaTest BreastCancerSelect. The recovered cDNA was tested for the presence of eCTCs and EMT-CTCs using the AdnaTests BreastCancerDetect and EMTDetect. Pts were considered CTC-positive if at least one of the two tests were positive. Statistical analysis included descriptive reporting, U-test for group differences, Rho correlations for dependencies and Fisher's chi-square test for distributional differences. Rho correlations were used to assess the relationship between NLR, PLR, MLR and tumor cells as well as progression-free survival (PFS) and overall survival (OS). Results: DTCs were detected in 34% of the pts and at least one CTC-subtype was found in 28% of the pts. Whereas the presence of DTCs was not associated with PFS or OS, the presence of CTCs significantly correlated with a shorter PFS (p=0.046) and OS (p=0.018). However, neither eCTCs nor EMT-CTSs alone were of prognostic significance. Enhanced lymphocyte (p=0.025) and monocyte counts (p=0.039) as well as a low PLR (p=0.032) significantly correlated with a reduced PFS in pts still alive whereas an enhanced MLR showed a high correlation with a shorter PFS (p=0.007) and OS (p=0.021) in deceased pts. Whereas MLR significantly correlated with the presence of EMT-CTCs (p=0.045), the presence of eCTCs significantly associated with an elevated NLR (p=0.003) and enhanced lymphocyte (p=0.007) as well as monocyte counts (p=0.012). No significant correlations were found for NLR, PLR and MLR with DTCs, however, DTC-positive pts, harboring a lower PLR, had a significant shorter OS (p=0.043). Conclusion: Here we show that proinflammatory markers in blood are closely related to the presence of different CTC subsets in early BC while no direct correlation was found for tumor cell spread to the bone. These findings might improve the prognostication of these pts and probably help to monitor response to therapy and adjust treatment options.
Citation Format: Sabine Kasimir-Bauer, Ebru Karaaslan, Olaf Hars, Ann-Kathrin Bittner, Oliver Hoffmann, Rainer Kimmig. In early breast cancer, the ratios of neutrophils, monocyctes and platelets to lymphocytes significantly correlate with the presence of subsets of circulating tumor cells in blood and disseminated tumor cells in the bone marrow [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-02-04.