Background. Cathepsin D is a lysosomal protease overexpressed and abnormally secreted in most breast cancer cells. Several retrospective clinical studies have shown that cathepsin D is an independent prognostic factor in breast cancer that is associated with a higher risk of recurrence and a shorter overall survival.
Methods. To the authors' knowledge, this is the first prospective study in which the prognostic value of cathepsin D was studied in 123 patients with primary breast cancer who were followed for 5 years between March 1985 and December 1990. Cathepsin D concentrations in breast cancer cytosol were measured using a solid-phase sandwich immunoenzymatic assay. The most significant prognostic factors were identified by multivariate analysis using the Cox proportional-hazards method.
Results. The median value of cathepsin D was 20.8 pmol/mg of protein, which was approximately half than the median value found in subsequent assays done using a commercially available kit and reported in most retrospective studies. The cathepsin D status or level was correlated only with axillary lymph node involvement. A univariate analysis showed that high levels of cathepsin D (> 20 pmol/mg of protein) were correlated with a higher risk of recurrence and a shorter overall survival (P < 0.01 and P < 0.03, respectively). Using multivariate analysis, a high cathepsin D level, a negative progester-From the *INSERM U 148 and the $Centre Paul Lamarque, Val d'Aurelle, Parc EuromPdecine, Montpellier, and the