Clinical Significance of Cathepsin D Concentration in Tumor Cytosol of Primary Breast Cancer

2005 ◽  
Vol 20 (2) ◽  
pp. 103-111 ◽  
Author(s):  
J. Rodríguez ◽  
J. Vízquez ◽  
M.D. Corte ◽  
M. Lamelas ◽  
M. Bongera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Primary Breast Cancer ◽  
Cathepsin D ◽  
Prognostic Significance ◽  
Immunoradiometric Assay ◽  
Breast Cancer Patients ◽  
Node Positive ◽  
Wide Range ◽  
Cause Specific Survival

Background Cathepsin D is the proteolytic enzyme most frequently implicated as a prognostic factor in primary breast cancer. In the present study we evaluated by means of an immunoradiometric assay the tumor content of this protease in primary breast cancer, its relationship with tumor-related clinical and pathological parameters, and its prognostic significance in a large series of breast cancer patients. Method The study comprised 1033 women with histologically established invasive breast cancer. Cathepsin D was measured in cytosol samples by means of an immunoradiometric assay to determine the total amount of cathepsin D (52 kDa, 48 kDa and 34 kDa). Evaluation of relapse-free survival and cause-specific survival was performed in the group of 1003 patients without evidence of metastasis at the time of initial diagnosis. The median follow-up of the patients who were free of recurrence was 54 months. Results Cathepsin D levels showed a wide range among the studied tumors (n=1033; median (range) 41 (0.9–2504) pmol/mg protein). Statistical analysis showed that the median cathepsin D levels were considerably higher in large tumors (T2–4) than in smaller ones (T1) (p=0.017), as well as in node-positive than in node-negative tumors (p=0.004). Cathepsin D levels were also higher in ductal tumors than in the other histological types (p=0.001), as well as in moderately or poorly differentiated tumors (p<0.001). Likewise, the median value of the protease was significantly higher in ER or PgR-positive tumors than in hormone receptor-negative ones (p=0.011 and p=0.004, respectively), as well as in aneuploid tumors than in diploid tumors (p=0.029). Multivariate analysis demonstrated that elevated cathepsin D levels (>59 pmol/mg protein) were notably associated with a shorter cause-specific survival in the whole group of patients with breast cancer, as well as in the subgroup of node-positive patients (p<0.05). Conclusions This study suggests that elevated intratumoral cathepsin D levels may identify a subset of node-positive breast cancer patients showing a high probability of earlier death.

Prognostic significance of PAI-1 and uPA in cytosolic extracts obtained from node-positive breast cancer patients

1997 ◽  
Vol 43 (2) ◽  
pp. 153-163 ◽  
Author(s):  
Jan Grøndahl-Hansen ◽  
Susan G. Hilsenbeck ◽  
Carle Christensen ◽  
Gary M. Clark ◽  
C. Kent Osborne ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Breast Cancer Patients ◽  
Node Positive ◽  
Pai 1 ◽  
Positive Breast Cancer

Prognostic significance of dna-ploidy in a series of 690 primary breast cancer patients

1990 ◽  
Vol 45 (1) ◽  
pp. 34-39 ◽  
Author(s):  
H. Beerman ◽  
Ph. M. Kluin ◽  
J. Hermans ◽  
C. J. H. Van de Velde ◽  
C. J. Cornelisse
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Primary Breast Cancer ◽  
Dna Ploidy ◽  
Prognostic Significance ◽  
Breast Cancer Patients

Cathepsin D by western blotting and immunohistochemistry: failure to confirm correlations with prognosis in node-negative breast cancer.

1994 ◽  
Vol 12 (3) ◽  
pp. 467-474 ◽  
Author(s):  
P M Ravdin ◽  
A K Tandon ◽  
D C Allred ◽  
G M Clark ◽  
S A Fuqua ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibody ◽  
Cancer Patients ◽  
Western Blotting ◽  
Cathepsin D ◽  
Prognostic Significance ◽  
Polyclonal Antiserum ◽  
Breast Cancer Patients ◽  
Node Negative ◽  
Tumor Bank

PURPOSE We attempted to replicate and improve on our previous study (N Engl J Med 322:297-302, 1990) that showed that 34-kd cathepsin D levels as determined by Western blotting strongly correlated with disease-free survival (DFS) and overall survival (OS) of axillary node-negative (N-) breast cancer patients. We also examined the prognostic significance of cathepsin D measured by immunohistochemistry (IHC) in these patients. PATIENTS AND METHODS Western blotting was performed on cytosols from frozen tumor specimens of 927 N- breast cancer patients in the San Antonio Breast Tumor Bank. The monoclonal antibody M1G8 was used to detect cathepsin D (in previous study, a polyclonal antiserum had been used). The same monoclonal antibody was also used for frozen-section IHC staining of tumor specimens from 562 N- patients from the same tumor bank. Levels of cathepsin D expression were then correlated with DFS and OS. RESULTS Although the levels of cathepsin D expression as measured by Western blotting and IHC correlated with each other and with levels of cathepsin D measured in previous work using Western blotting with the polyclonal antiserum, in this present study, using the monoclonal antibody M1G8, we were unable to demonstrate that cathepsin D expression (measured by either Western blotting or by IHC) correlates with DFS or OS. CONCLUSION In this study, cathepsin D expression as determined by either Western blotting or IHC using the monoclonal antibody M1G8 failed to improve the prognostic evaluation of N- breast cancer patients. The role of cathepsin D expression as a prognostic factor is still not precisely defined, raising questions about its use in the routine evaluation of N- breast cancer patients.

Prognostic relevance of induced and spontaneous apoptosis of disseminated tumor cells in primary breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21003-e21003
Author(s):  
Andreas D. Hartkopf ◽  
Malgorzata Banys ◽  
Gerhard Gebauer ◽  
Natalia Krawczyk ◽  
Markus Hahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Survival Data ◽  
Primary Breast Cancer ◽  
Neoadjuvant Treatment ◽  
Prognostic Significance ◽  
Disseminated Tumor Cells ◽  
Apoptotic Cells ◽  
Breast Cancer Patients

e21003 Background: An imbalance between cell proliferation and programmed cell death leads to tumor growth. Although most cytostatic agents used in systemic therapy of breast cancer induce an apoptosis in tumor cells leading to their destruction, a high ratio of apoptotic cells in primary breast cancer is correlated with poor prognosis. The purpose of this study was to investigate the incidence and prognostic significance of apoptotic disseminated tumor cells (DTC) in bone marrow (BM) of primary breast cancer (PBC) patients. Methods: PBC patients who underwent primary surgery (PS) or were treated with neoadjuvant chemotherapy (NACT) between 01/2003 and 12/2007 were included into this prospective study. BM aspirates were analyzed by immunocytochemistry (M30 antibody) using ACIS system (Chromavision) according to the ISHAGE evaluation criteria. Patients without DTC in the BM were excluded from the study. Survival data were evaluated after a median follow up of 44 months. Results: BM aspirates of 383 PBC patients were analyzed. DTC were M30 positive in 82 of 298 (27%) patients who underwent PS and 41 of 85 (48%) patients treated with NACT. After NACT, the incidence of apoptotic cells in patients with complete/partial remission as compared to patients with stable/progressive disease was 63%/53% vs. 31%/0% (p=0.034). In the NACT group, M30-positive patients suffered less likely of a relapse than those without apoptotic DTC (7% vs. 23% of the events, p = 0.049). Inversely, overall survival in the PS group was significantly shorter in M30-positive as compared to M30-negative patients (75 months, 95% CI: 68-81 months vs. 84 months, 95% CI: 81-86 months; p = 0.008). Conclusions: Apoptotic DTC can be detected in breast cancer patients before and after systemic treatment. The presence of apoptotic DTC in BM of breast cancer patients can reflect the effects of neoadjuvant treatment. Spontaneous and chemotherapy-induced apoptosis may have different prognostic implications.

scholarly journals International Collaborative Cancer Group (ICCG)

2006 ◽  
Vol 9 (S1) ◽  
pp. 287-301
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Randomized Trial ◽  
Cancer Patients ◽  
Primary Breast Cancer ◽  
Breast Cancer Patients ◽  
Double Blind ◽  
Node Positive ◽  
Cancer Group ◽  
International Collaborative

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by International Collaborative Cancer Group (ICCG). Clinical trials include: Epirubicin plus tamoxifen versus tamoxifen alone in postmenopausal node-positive primary breast cancer. C/4/87Adjuvant cyclophosphamide methotrexate and 5-fluorouracil (CMF) versus 5-fluorouracil, epirubicin and cyclophosphamide (FEC) in premenopausal node-positive primary breast cancer. (CMF/FEC N+). C/2/84Adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) versus 5-fluorouracil, epirubicin and cyclophosphamide (FEC) in women with node-negative, poor-risk primary breast cancer. C/6/89Adjuvant FEC50 versus FEC75 with or without the additional benefit of sequential hormone therapy (HT) in node-positive premenopausal primary breast cancer. C/9/91High-dose therapy with PBCS support in primary breast cancer. C/10/92 – C/32/96Randomized double-blind trial in postmenopausal women with primary breast cancer who have received adjuvant tamoxifen for 2–3 years, comparing subsequent adjuvant exemestane treatment with further tamoxifen. BIG 02-97/Study No. 96 OEXE 031-C/13/96A multicentre-randomized trial of sequential epirubicin and docetaxel versus epirubicin in node-positive postmenopausal breast cancer patients. C/14/96A phase III multicentre double-blind randomized trial of celecoxib versus placebo in primary breast cancer patients. An intergroup study from the International Collaborative Cancer Group and the German Breast Group (GBG). BIG 1-03 – ICCG/C/20/01 – GBG 27

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