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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 anti-inflammatory agents were recruited from four Ontario hospitals. Women provided fasting blood for measurement of metabolic, inflammatory, and tumor markers 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-later-line therapy (38.5%). CTC counts (per 7.5 mL of blood) ranged from 0 to 1238 (median 2); an elevated CTC count, defined as five or more CTCs, was detected in 42 (43.8%) patients. Those with liver metastases (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 body mass 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.
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Details
1 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System; Department of Medicine, University of Toronto, Toronto, ON, Canada
2 University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada
3 Applied Statistician, Markham, ON, Canada
4 Department of Medicine, University of Toronto, Toronto, ON, Canada; University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada
5 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System; Department of Medicine, University of Toronto, Toronto, ON, Canada; University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada
6 Department of Medicine, University of Toronto, Toronto, ON, Canada; St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada
7 London Regional Cancer Program, London, ON, Canada
8 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System
9 Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada
10 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada