Development of a novel metastatic breast cancer score based on hyaluronic acid metabolism

Tumor metastasis involves the dissemination of malignant cells into the basement membrane, and the vascular system contributes to the circulating pool of these markers. In this context, our aim has been focused on the development of a non-invasive score based on degradation of the backbone of glycosaminoglycans of the extracellular matrix; namely hyaluronic acid (HA), for the assessment of metastasis in patients with breast cancer. HA level was determined by enzyme-linked immunosorbent assay; CA 15.3 was determined by microparticle enzyme immunoassay; hyaluronidase, N-acetyl-β-d-glucosaminidase, β-glucuronidase, glucuronic acid, and glucosamine were assayed by standard colorimetric techniques in 217 patients with breast cancer. Statistical analyses were performed by logistic regression and receiver-operating characteristic analysis curves. The multivariate discriminant analysis selects a score based on absolute values of the six biochemical markers: metastatic breast cancer score (MBCS) = [1.04 (Numerical constant) + 0.003 × CA 15.3 (U/l) + 0.001 × HA (ng/ml) + 0.004 × hyaluronidase (mg N-acetyl-β-d-glucosamine/ml/18 h) + 0.001 × N-acetyl-β-d-glucosaminidase (μmol/ml/min) + 0.026 × glucuronic acid (ng/ml) + 0.003 × glucosamine (μg/dl)]. This function correctly classified 87 % of metastatic breast cancer at cut-off value = 0.85 (i.e., great than 0.85 indicates patients with metastatic breast cancer and less than 0.85 indicates patients with non-metastatic breast cancer). MBCS is a novel, non-invasive, and simple score which can be applied to discriminate patients with metastatic breast cancer.