A. Monastirioti (Heraklion, Greece)
University of CreteAuthor Of 1 Presentation
25P - Investigation of TLR4 and pSTAT3 expression on circulating tumor cells (CTCs) in patients with metastatic breast cancer (mBC)
Abstract
Background
Toll-like receptor 4 (TLR4) and phosphorylated signal transducer and activator of transcription protein 3 (pSTAT3) hold a key role in inflammatory response and promote tumor immune escape upon expression on tumor cells. We evaluated the incidence and clinical relevance of CTCs expressing TLR4 and/or pSTAT3 in patients with mBC.
Methods
Peripheral blood was obtained from 100 mBC patients (recurrent: n=72; de novo metastatic: n=28) prior to first-line therapy. Triple immunofluorescence staining for cytokeratins (CK), TLR4 and pSTAT3 was performed on peripheral blood mononuclear cell cytospins. CK+ CTCs were characterized for TLR4 and pSTAT3 expression using the Ariol microscopy system.
Results
CK+ CTCs (n=28) were detected in 19 out of 100 patients. TLR4+ CTCs and pSTAT3+ CTCs were detected in 13% and 14% of patients, respectively, and represented the 53.6% and 60.7% of total CK+ CTCs, respectively. TLR4+/pSTAT3+ CTCs prevailed in patients with triple-negative BC (n=12), as compared to hormone receptor-positive/HER2-negative and HER2-positive subtypes (25%, 9.5% and 0%, respectively, p=0.033). The detection of CK+ CTCs was predictive for shorter OS (median: 24.9 vs 36.5 months; p=0.042; Kaplan Meier), whereas the detection of TLR4+ CTCs was associated with shorter PFS (median: 11.4 vs 12.6 months; p=0.036). In the de novo mBC setting, lower survival rates were encountered for patients harboring TLR4+ CTCs (median PFS: 9.6 vs 20.8 months; p=0.024), or pSTAT3+ CTCs (median PFS: 3.4 vs 20.8 months; p=0.006; median OS: 19 vs 60.8 months; p=0.005), and especially those with TLR4+ and/or pSTAT3+ CTCs (median PFS: 9.6 vs 31.9 months; p=0.003; median OS: 23.1 vs 74.8; p=0.014).
Conclusions
These results provide first evidence on the expression of TLR4 and pSTAT3 at the CTC-level in breast cancer (BC) with clinical relevance, implying that TLR4/STAT3 signaling pathways may have a role in BC progression. CTC detection and phenotyping according to TLR4 and pSTAT3 expression could serve for the refinement of prognosis in mBC.
Legal entity responsible for the study
Sofia Agelaki, Associate Professor of Medical Oncology, UoC.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.