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High Serum YKL-40 Levels in Patients with Primary Breast Cancer is Related to Short Recurrence Free Survival

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Abstract

YKL-40 is a growth factor for connective tissue cells and stimulates migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum YKL-40 in patients with metastatic breast cancer and colorectal cancer is associated with a poorer prognosis as compared to patients with normal serum YKL-40. In the present study we evaluated the associations of preoperative serum YKL-40 in 271 patients with primary breast cancer in relation to relapse-free survival and overall survival. The median follow-up time was 5.9 years. There were 77 relapses and 69 patients died. The median serum YKL-40 concentration in the patients was 57 µg/l (range 22–688 µg/l) and significantly elevated (p < 0.0001) compared to serum YKL-40 in healthy females. Nineteen percent of the patients had high serum YKL-40 (i.e., > 95 percentile of healthy females). Patients with high serum YKL-40 had shorter relapse-free interval (hazard ratio (HR) = 1.77, 95% confidence interval (CI): 1.06–2.95, p = 0.028) and overall survival (HR = 1.78, 95% CI: 1.04–3.05, p = 0.036) than patients with normal serum YKL-40. Serum YKL-40 was higher (p = 0.005) in lymph node positive patients as compared to lymph node negative patients. Multivariate analysis including lymph node status, estrogen receptor status, tumor size, age, menstrual status and serum YKL-40 showed that serum YKL-40 was an independent prognostic variable of relapse-free survival (HR = 1.73, 95% CI: 1.03–2.91, p = 0.039). Our results show that serum YKL-40 in patients with primary breast cancer at time of operation is only elevated in a small group of patients, but these patients have a shorter recurrence free interval. Further studies are required to determine the biological function of YKL-40 in breast cancer.

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Author notes

  1. Nils Brünner

    Present address: Institute of Pharmacology and Pathobiology, Royal Veterinary and Agriculture University, Frederiksberg, Denmark

Authors and Affiliations

  1. Connective Tissue Laboratory, Department of Rheumatology, H:S Hvidovre Hospital, University of Copenhagen, Denmark

    Julia S. Johansen

  2. Finsen Laboratory, H:S Rigshospitalet, University of Copenhagen, Denmark

    Ib J. Christensen, Rikke Riisbro & Nils Brünner

  3. Department of Surgery, John Radcliff Hospital, Oxford, England

    Michael Greenall

  4. Imperial Cancer Research Fund, Molecular Oncology Laboratories, Institute of Molecular Medicine, Oxford, England

    Chen Han, Kenneth Smith & Adrian L. Harris

  5. Department of Biology, University of California San Diego, La Jolla, California, USA

    Paul A. Price

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Johansen, J., Christensen, I.J., Riisbro, R. et al. High Serum YKL-40 Levels in Patients with Primary Breast Cancer is Related to Short Recurrence Free Survival. Breast Cancer Res Treat 80, 15–21 (2003). https://doi.org/10.1023/A:1024431000710

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