Prognostic impact of cathepsin D and c-erbB-2 oncoprotein in a subgroup ofnode-negative breast cancer patients with low histological grade tumors

Some node-negative breast cancer patients, with initially good prognosis, r elapse from their cancer and are poorly identified. In the present study, b ased on prospective data of 197 tumors, we measured cathepsin D (cath D, n= 197), pS2 protein (n=125), c-erbB-2 oncoprotein (n=100) and epidermal growt h factor receptor (EGF-R, n=99) to better define the risk of relapse of nod e-negative patients in comparison with that defined by the clinical and his tological factors, The median follow-up in surviving patients was 75 months . Univariate analysis indicated that patients with histological grade III t umors (the Scarff, Bloom and Richardson classification) had a much poorer p rognosis than those with histological grade I or II tumors (P=0.0027 for re lapse-free survival and P=0.0156 for overall survival). When the population of node-negative patients was divided by tertiles, high cath D levels show ed a significant association with an early relapse (P=0.0316). Using cut-of f values, patients with high cath D (greater than or equal to 25 pmol/mg pr otein) or c-erbB-2 oncoprotein (greater than or equal to4 Human Neu Unit/mu g protein) levels, had a significant worse relapse-fi ee survival(P=0.0147 and 0.0417, respectively). No prognostic information was supported by pS2 p rotein or EGF-R measurements. In multivariate analysis, histological grade, cath D and c-erbB-2 oncoprotein remained independent predictors of recurre nce (P=0.005, 0.0361 and 0.0321, respectively). By combining low levels of cath D and c-erbB-2 oncoprotein in histological grade I or II tumors, we id entified a subgroup of patients with a 100% relapse-free survival probabili ty at 6 years of follow-up. Moreover, the subgroup of patients with histolo gical grade I or II tumors and high values of both cath D and c-erbB-2 onco protein showed a prognosis as poor as the subgroup defined by histological grade III alone, respectively 66% and 70% relapse-free survival at 6 years of follow-up. In conclusion, the combination of conventional prognostic fac tor (histological grade) and biochemical factors (cath D and c-erbB-2 oncop rotein) enabled us to identify, in this preliminary study, a subgroup of pa tients having an increased risk of relapse in a group (node-negative patien ts with low histological grade tumors) considered as good prognosis.