A novel discriminant score based on tumor-associated trypsin inhibitor for accurate diagnosis of metastasis in patients with breast cancer.

Invasion and metastasis of solid tumors require proteolytic enzymes for degradation of the basal membrane and extracellular matrix. Currently, there are no reliable methodologies to predict the risk for metastatic disease. In this context, our aim has been focused on the development of a noninvasive score based on tumor-associated trypsin inhibitor (TATI) for the assessment of metastasis in patients with breast cancer. TATI, trypsin, and soluble epidermal growth factor receptor (sEGFR) were assayed by enzyme-linked immunosorbent assay. CA 15.3 serum level was assayed by microparticle enzyme immunoassay in 265 patients with breast cancer. Statistical analyses were performed by logistic regression and receiver operating characteristic analysis curves. Using multivariate discriminant analysis, a score is selected based on absolute values of the four biochemical markers: TATI-metastatic breast cancer score (TATI-MBCS) = [0.03 × CA 15.3 (U/L) + 0.039 × TATI (ng/ml) + 0.04 × trypsin (ng/ml) + 0.023 × sEGFR (ng/ml) - 6.49 (numerical constant)]. This function correctly classified 84% of metastatic breast cancer at cutoff value = 0.62 (i.e., greater than 0.62 indicates patients with metastatic breast cancer and less than 0.62 indicates patients with nonmetastatic breast cancer). In conclusion, TATI-MBCS is a novel, noninvasive, and simple score which can be applied to discriminate patients with metastatic breast cancer.