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High Levels of Serum HER-2/neu and YKL-40 Independently Reflect Aggressiveness of Metastatic Breast Cancer

Department of Oncology, Herlev Hospital [B. V. J., J. S. J.], and Department of Rheumatology [J. S. J.], Hvidovre Hospital, University of Copenhagen, DK-2750 Herlev Denmark, and Department of Biology, University of California, San Diego, La Jolla, California [P. A. P.]

Purpose: To evaluate serum levels of HER2 (an epithelial growth factor) and YKL-40 (a growth factor participating in inflammation and remodeling of the extracellular matrix) in relation to outcome in patients with their first diagnosis of recurrent breast cancer.

Design: Serum HER2 and YKL-40 levels were measured in 100 patients referred with their first metastatic manifestation of breast cancer before first line anthracycline-based therapy and related to response to therapy, metastatic pattern, time to progression, and overall survival. During the observation period of 64–84 months, 89 patients died of breast cancer.

Results: The patients had higher serum HER2 and YKL-40 levels than healthy females (P < 0.0001). Serum HER2 was elevated in 32% of the patients and serum YKL-40 in 30%. These patients were more sick (P < 0.01) and more often had parenchymal involvement (P < 0.0005), especially liver metastases (P < 0.00005). In multivariate Cox analysis, high serum levels of HER2 or YKL-40 or lack of estrogen receptors independently doubled the relative risk of progression and dying (P < 0.001) even after accounting for other independent prognostic variables, such as axillary nodal involvement at primary diagnosis, liver metastases, and more than two metastatic sites. Fewer patients with high serum HER2 or YKL-40 or lack of estrogen receptors responded with a complete remission on chemotherapy (P = 0.005, 0.036, and 0.006). In these patients, high serum YKL-40 was a stronger predictor of survival than high serum HER2 or lack of estrogen receptors.

Conclusions: High serum HER2 and YKL-40 independently identified subgroups of patients with metastatic breast cancer with a poor prognosis.

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