Estrogen-regulated cut-off values of pS2 and cathepsin D expression in breast carcinomas

The purpose of the study was to asses the expression of estrogen-induced pS2 and cathepsin D (CD) that might facilitate biological subgrouping of patients with breast carcinomas (BC) and its potential applicability in clinical oncology. The study included 226 patients with histologically verified BC. Clinico-pathological findings were classified according to age, menopausal status, tumor size, histologic grade, and regional lymph node status. Estrogen and progesterone receptors (ER and PR), as well as CD and pS2 protein concentrations were assayed on the same cytosolic extract in accordance with the recommendation of EORTC. Statistically significant direct correlations were observed between CD expression and axillary node status and between pS2 expression and histologic grade, while the expression of both proteins was related to both ER and PR status. Baseline levels of CD expression were found in patients with SR-negative status and node-negative or tumors less than 2cm. Unfavorable carcinoma subgroups, in relation to pS2 expression, were defined as pre- and postmenopausal carcinomas with histologic grade III. The highest CD level observed in SR-negative unfavorable subgroups (38.7 pmol/mg) and the highest pS2 level observed in ER(-) unfavorable subgroups (14.7 ng/mg) were considered as the cut-off values. These values defined estrogen-regulated expression of CD and pS2 protein that might enable the identification of patients at high risk of disease progression, for whom more aggressive adjuvant approach would be warranted, as well as the identification of patients whose prognosis is so good that adjuvant therapy would not be cost-beneficial.