Document Detail


High survivin predicts a poor response to endocrine therapy, but a good response to chemotherapy in advanced breast cancer.
MedLine Citation:
PMID:  16541327     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Variants of survivin with differing subcellular localizations might mediate the different functions of survivin, i.e. cell-cycle regulation and apoptosis inhibition. Highly proliferative tumors are more sensitive to chemotherapy, whereas apoptosis resistant cells would be refractory to endocrine therapy. Possibly, this explains incongruent data on the association of survivin with prognosis in breast cancer. Survivin levels were measured using ELISA in 800 x g pellets and 100,000 x g supernatants of breast cancer tissues from patients that were treated with either chemotherapy or endocrine therapy for advanced disease. These fractions might be enriched with nuclear or cytoplasmatic located survivin variants. Survivin levels were associated with tumors with poor prognostic clinical characteristics. For the patients treated with endocrine therapy, the patients with high survivin levels exhibited a significantly shorter progression free survival (PFS) than those who had low levels (pellet survivin Hazard Ratio (HR)=2.74, 95% Confidence Interval (CI)=1.31-5.72, p=0.008 and median PFS 5.8 versus 8.6 months, p=0.006, log-rank; cytosolic survivin HR=3.03, 95% CI=1.45-6.35, p=0.003). In contrast, for patients treated with chemotherapy, those with high cytosolic survivin had a significantly longer PFS than those with low levels (median PFS of 6.2 months, versus 4.7 months for patients with low cytosolic concentrations, p=0.024, log-rank). Thus, high levels of survivin are mainly related with a poor response to endocrine therapy, but a good response to chemotherapy. This phenomenon might be related to the different functions of survivin.
Authors:
Paul N Span; Vivianne C G Tjan-Heijnen; Peggy Manders; Doorlene van Tienoven; Jeffrey Lehr; Fred C G J Sweep
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Publication Detail:
Type:  Journal Article     Date:  2006-03-16
Journal Detail:
Title:  Breast cancer research and treatment     Volume:  98     ISSN:  0167-6806     ISO Abbreviation:  Breast Cancer Res. Treat.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-07-12     Completed Date:  2006-10-26     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8111104     Medline TA:  Breast Cancer Res Treat     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  223-30     Citation Subset:  IM    
Affiliation:
Department of Chemical Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. p.span@ace.umcn.nl
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Aromatase Inhibitors / therapeutic use
Breast Neoplasms / chemistry,  drug therapy*,  mortality
Enzyme-Linked Immunosorbent Assay
Female
Humans
Medroxyprogesterone Acetate / therapeutic use
Microtubule-Associated Proteins / analysis*
Middle Aged
Neoplasm Proteins / analysis*
Tamoxifen / therapeutic use
Chemical
Reg. No./Substance:
0/Aromatase Inhibitors; 0/BIRC5 protein, human; 0/Microtubule-Associated Proteins; 0/Neoplasm Proteins; 10540-29-1/Tamoxifen; 71-58-9/Medroxyprogesterone Acetate

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