A prospective study of the prognostic value of cathepsin D levels in breast cancer cytosol.
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 progesterone receptor status, and lymph node involvement were the most important factors for predicting relapse-free survival (P = 0.02, P < 0.01, and P < 0.05, respectively). The cathepsin D level had prognostic value in patients with node-positive disease (P = 0.001) and appeared to be particularly useful in association with the progesterone receptor status by isolating a high-risk subgroup of patients (high cathepsin D level; negative progesterone receptor status).


CONCLUSIONS
This first prospective study confirmed the prognostic value of the cathepsin D level in association with other major prognostic factors. The next step will be to determine whether the subset of patients with high cathepsin D levels would benefit from adjuvant therapy.
Pujol
P
P
INSERM U 148, Montpellier, France.
Maudelonde
T
T
Daures
J P
JP
Rouanet
P
P
Brouillet
J P
JP
Pujol
H
H
Rochefort
H
H
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality; D002402:Cathepsin D / Q000032:analysis*; D003600:Cytosol / Q000201:enzymology*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
D002402:Cathepsin D