Association of metabolic, inflammatory, and tumor markers with circulating tumor cells in metastatic breast cancer

Abstract

Background: Circulating tumor cells (CTCs) are associated with worse prognosis in metastatic breast cancer (BC). We evaluated the association of metabolic, inflammatory, and tumor markers with CTCs in women with metastatic BC before commencing a new systemic therapy. Methods: Ninety-six patients with newly diagnosed or progressing metastatic BC without current diabetes or use of antiinflammatory agents were recruited fromfour Ontario hospitals.Women provided fasting blood formeasurement ofmetabolic, inflammatory, and tumormarkers and CTCs. CTCs were assayed within 72 hours of collection using CellSearch. Other blood was frozen at -80°C, and assays were performed in a single batch. Associations between CTC counts with study factors were evaluated using Spearman correlation, and the chi-square or Fisher exact test. All statistical tests were two-sided and P value ≤.05 was considered statistically significant. Results: The median age was 60.5 years; 90.6% were postmenopausal. The cohort included hormone receptor-positive (87.5%), HER2-positive (15.6%), and triple-negative (10.4%) BCs. Patients were starting firstline (35.5%), second-line (26.0%), or third-or-laterline therapy (38.5%). CTC counts (per 7.5mL of blood) ranged from0 to 1238 (median 2); an elevated CTC count, defined as five or more CTCs, was detected in 42 (43.8%) patients. Those with livermetastases (vs not)more frequently had an elevated CTC count (59.0% vs 33.3%, P = .02). CTCs were significantly associated with C-reactive protein (R = .22, P = .02), interleukin (IL)-6 (R = .25, P = .01), IL-8 (R = .38, P = .0001), plasminogen activator inhibitor 1 (R = .31, P = .001), carcinoembryonic antigen (R = .31, P = .002), and cancer antigen 15-3 (R = .40, P = .0001) and inversely associated with bodymass index (R = -.23, P = .02) and leptin (R = -.26, P = .01). Conclusions: CTC counts were positively associated with tumor and inflammatory markers and inversely associated with some metabolic markers, potentially reflecting tumor burden and cachexia.