title: Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patients.
abstract: There is controversy regarding the prognostic value of cathepsin-D in primary breast cancer. An increased level of cathepsin-D in tumour extracts has been found to be associated with a poor relapse-free and overall survival. Studies performed with immunohistochemistry or Western blotting have produced diverse results. We have analysed 2810 cytosolic extracts obtained from human primary breast tumours for cathepsin-D expression, and have correlated their levels with prognosis. The median follow-up of the patients still alive was 88 months. Patients with high cathepsin-D levels had a significantly worse relapse-free and overall survival, also in multivariate analysis (P < 0.0001). Adjuvant therapy which was associated with an improved prognosis in node-positive patients in univariate analysis, also significantly added to the multivariate models for relapse-free and overall survival. There were no statistically significant interactions between the levels of cathepsin-D and any of the classical prognostic factors in analysis for relapse-free survival, suggesting that the prognostic value of cathepsin-D is not different in the various subgroups of patients. Indeed, multivariate analyses in subgroups of node-negative and -positive patients, pre- and post-menopausal patients, and their combinations, showed that tumours with high cathepsin-D values had a significantly poor relapse-free survival, with relative hazard rates ranging from 1.3 to 1.5, compared with tumours with low cathepsin-D levels. The results presented here on 2810 patients confirm that high cytosolic cathepsin-D values are associated with poor prognosis in human primary breast cancer.
authors.affiliation: Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek), Academic Hospital, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Foekens
authors.forename: M P
authors.initials: MP
authors.lastname: Look
authors.forename: J
authors.initials: J
authors.lastname: Bolt-de Vries
authors.forename: M E
authors.initials: ME
authors.lastname: Meijer-van Gelder
authors.forename: W L
authors.initials: WL
authors.lastname: van Putten
authors.forename: J G
authors.initials: JG
authors.lastname: Klijn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D002402:Cathepsin D / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012008:Recurrence; D012044:Regression Analysis
chemical_list: D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D002402:Cathepsin D