ABSTRACT
OBJECTIVE: The objective of this retrospective study was to define the prognostic value of cathepsin D (CD) in the node-negative (N-) and node-positive (N+) subsets of breast cancer (BC) patients. PATIENTS AND METHODS: In primary tumor cytosols of 348, stage I-III, BC patients, with a complete standard histological examination and a 56 months mean follow-up, the ER, PR and CD concentrations were measured by standardized assays. CD values were then compared to the classical prognostic factors, the type of treatment and the outcome, in terms of Disease-Free-Survival (DFS) and type of Relapse, after stratification according to the nodal status. Statistical methods used were Cox regression and logistic regression. RESULTS: Using univariate analysis, CD > 60 pmol/mg prot in N- patients was significantly associated with shorter DFS as well as local-regional recurrence (LRR) while in multivariate analysis the same CD levels, together with T status, are the best predictors of short DFS. However, CD > 60 is the only potent predictor of LRR in N- patients. No prognostic value of CD was identified in N+ patients. The cutoff value of CD should be 60 pmol/mgprot. The combination of tumor size, ER status and CD concentration may yield reliable prediction of primary BC outcome in N- patients. CONCLUSION: CD is a marker of invasiveness, particularly loco-regional in node-negative breast cancer. The integration of this marker, in the routine of initial prognostic evaluation of this subset of patients is proposed.
Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/chemistry , Breast Neoplasms/diagnosis , Cathepsin D/analysis , Neoplasm Recurrence, Local/diagnosis , Adult , Disease-Free Survival , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Middle Aged , Multivariate Analysis , Prognosis , Retrospective StudiesABSTRACT
In this study the unexpected findings from the analysis of 278 breast cancer tissue specimens are reported. A surprising strongly positive correlation between an unfavourable and a favourable prognosis with markers cathepsin D and pS2 respectively, was revealed by linear regression analysis (Pearson, Student-T-Test). In the relevant literature reviewed only one similar, although indirect, observation was found. On the other hand, a weak relationship between pS2 and ER has emerged using the same method, while the pS2/PgR association remained strong. The latter supports the hypothesis that pS2 positivity is associated with positive PgR and may be a marker of functioning ER, irrespective of ER status. These and other similar findings underline the need for a better understanding of the underlying molecular events as well as the necessity of an effective prognostic evaluation model for breast cancer.
Subject(s)
Breast Neoplasms/metabolism , Cathepsin D/metabolism , Proteins/metabolism , Receptors, Estrogen/metabolism , Adult , Biomarkers, Tumor/metabolism , Breast Neoplasms/diagnosis , Humans , Immunologic Techniques , Lymphatic Metastasis , Middle Aged , Prognosis , Regression Analysis , Trefoil Factor-1 , Tumor Suppressor ProteinsABSTRACT
One hundred and seventy three women were followed-up for a median of 62 months after surgery for Stage I-III breast cancer. The concentration of cathepsin D (CD) in tumor cytosols was compared to the standard prognostic factors for the disease and related to relapse free and overall survival and type of relapse. Three groups were identified with different prognostic profile. High CD levels significantly shorten DFS in both node-negative and node-positive patients; a correlation between high cathepsin D levels and locoregional relapse should also be noted. This marker should be included in the initial evaluation of breast cancer as an indicator of invasiveness.
