PROGNOSTIC VALUE OF PS2 AND CATHEPSIN-D IN 710 HUMAN PRIMARY BREAST-TUMORS - MULTIVARIATE-ANALYSIS

Purpose: Evaluation of the prognostic value of cytosolic PS2 (pS2 protein) and cathepsin D in a large series of breast cancer patients by multivariate analysis taking into account steroid receptors and conventional prognostic factors. Patients and Methods: Prognostic factors were analyzed in 710 primary breast cancers (median follow-up, 4 years). PS2 and cathepsin D were measured by radiometric immunoassays. Estrogen receptor (ER) and progesterone receptor (PgR) status were assessed by radioligand binding assays and multiple-point Scatchard analysis. Results: The best cutoff point for PS2 to discriminate between positive (61% of the tumors) and negative was 2 ng/mg protein (univariate P value in 5-year relapse-free survival = .003). For cathepsin D, no sensible cutoff point could be chosen, since there was a continuous association between the level of cathepsin D and relapse rate (P = .001). In Cox multivariate analysis, relapse rate decreased with age of premenopausal/perimenopausal patients and with PS2 or steroid receptor positivity, and increased with the size of the tumor, the number of positive lymph nodes, and increasing levels of cathepsin D. In analysis for overall survival, age of both premenopausal/perimenopausal and postmenopausal patients, tumor size, the number of positive lymph nodes, ER/PgR, and PS2 were all independently associated with the rate of death. The level of cathepsin D was positively correlated with the rate of death, but this trend was not statistically significant. Separate Cox multivariate analyses for relapse-free survival in subgroups of patients as defined by nodal status showed that the contribution of PS2 and cathepsin D was the strongest in the node-negative subgroup. Node-negative patients with tumors containing PS2 values ≤ 2 ng/mg protein and cathepsin D values more than 70 pmol/mg protein experienced a 4.5-fold increase in relapse rate as compared with those with PS2 levels greater than 2 ng/mg protein and cathepsin D levels ≤ 30 pmol/mg protein. Conclusion: PS2 and cathepsin D are independent prognostic factors in primary breast cancer and lymph node-negative patients.