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A prospective study of the prognostic value of cathepsin D levels in breast cancer cytosol
Author(s) -
Pujol Pascal,
Maudelonde Thierry,
Daures JeanPierre,
Rouanet Philippe,
Brouillet JeanPaul,
Pujol Henri,
Rochefort Henri
Publication year - 1993
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19930315)71:6<2006::aid-cncr2820710614>3.0.co;2-q
Subject(s) - cathepsin d , medicine , breast cancer , oncology , cathepsin l , prospective cohort study , proportional hazards model , lymph node , cathepsin , hazard ratio , univariate analysis , cancer , multivariate analysis , gastroenterology , biology , enzyme , confidence interval , biochemistry
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 retro‐spective 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‐one 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.