| Abstract | PURPOSE: The aim of the study was to evaluate the predictive value of HER2 and topoisomerase IIalpha gene (TOP2A) for the efficacy of epirubicin in the adjuvant setting of breast cancer patients. PATIENTS AND METHODS: In the Danish Breast Cancer Cooperative Group trial 89D, 980 pre- and postmenopausal primary patients were randomly allocated to either CMF (cyclophosphamide, methotrexate, and fluorouracil; n = 500) or CEF (cyclophosphamide, epirubicin, and fluorouracil; n = 480) times 9, between January 1990 and November 1999. Tumor tissue was retrospectively identified from 805 patients and was analyzed for HER2-positivity and for TOP2A-amplifications and deletions. RESULTS: HER2-positivity was found in 33% of the 805 investigated tumors and was not a predictive marker for epirubicin sensitivity. TOP2A changes were identified in 23% of the 773 investigated tumors: 12% had TOP2A amplifications and 11% had TOP2A deletions. We found that patients with TOP2A amplification had an increased recurrence-free (RFS; hazard ratio [HR], 0.43; 95% CI, 0.24 to 0.78) and overall survival (OS; HR, 0.57; 95% CI, 0.29 to 1.13), respectively if treated with CEF compared with CMF, and that patients with TOP2A deletions had an almost identical hazard ratio (RFS: HR, 0.63; 95% CI, 0.36 to 1.11; OS: HR, 0.56; 95% CI, 0.30 to 1.04). This is in contrast to patients with a normal TOP2A genotype for whom similar outcome was observed in both treatment arms (RFS: HR, 0.90; 95% CI, 0.70 to 1.17; OS: HR, 0.88; 95% CI, 0.66 to 1.17). CONCLUSION: TOP2A amplification-and possibly deletion-seems to be predictive markers for the effect of adjuvant epirubicin containing therapy in primary breast cancer, but a final conclusion has to await a confirmative study or a meta-analysis. |
| Authors | Ann S Knoop, Helle Knudsen, Eva Balslev, Birgitte B Rasmussen, Jens Overgaard, Kirsten V Nielsen, Andreas Schonau, Katrín Gunnarsdóttir, Karen E Olsen, Henning Mouridsen, Bent Ejlertsen, Danish Breast Cancer Cooperative Group
(Affiliation: Oncological Department, Odense University Hospital DK-5000, Odense C, Denmark. knoop at dadlnet.dk)
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| Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 23
Issue 30
Pg. 7483-90
(Oct 20 2005)
ISSN: 0732-183X United States |
| PMID | 16234514
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)
|
| Chemical References |
- Antigens, Neoplasm
- CMF regimen
- DNA-Binding Proteins
- FEC protocol
- Isoenzymes
- Tumor Markers, Biological
- Cyclophosphamide
- Fluorouracil
- Epirubicin
- Methotrexate
- Receptor, erbB-2
- DNA Topoisomerases, Type II, Eukaryotic
- DNA topoisomerase II alpha
|
| Topics |
- Antigens, Neoplasm
(genetics)
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Breast Neoplasms
(drug therapy, genetics)
- Chemotherapy, Adjuvant
- Cyclophosphamide
(therapeutic use)
- DNA Topoisomerases, Type II, Eukaryotic
(genetics)
- DNA-Binding Proteins
(genetics)
- Epirubicin
(therapeutic use)
- Female
- Fluorouracil
(therapeutic use)
- Gene Amplification
- Gene Deletion
- Humans
- In Situ Hybridization, Fluorescence
- Isoenzymes
- Methotrexate
(therapeutic use)
- Predictive Value of Tests
- Premenopause
- Receptor, erbB-2
(genetics)
- Retrospective Studies
- Stereoisomerism
- Treatment Outcome
- Tumor Markers, Biological
(genetics)
|
