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.
RCT Entities:
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 cancerpatients. 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: Franca Podo; Lutgarde M C Buydens; Hadassa Degani; Riet Hilhorst; Edda Klipp; Ingrid S Gribbestad; Sabine Van Huffel; Hanneke W M van Laarhoven; Jan Luts; Daniel Monleon; Geert J Postma; Nicole Schneiderhan-Marra; Filippo Santoro; Hans Wouters; Hege G Russnes; Therese Sørlie; Elda Tagliabue; Anne-Lise Børresen-Dale Journal: Mol Oncol Date: 2010-04-24 Impact factor: 6.603
Authors: Michael F Press; Guido Sauter; Marc Buyse; Leslie Bernstein; Roberta Guzman; Angela Santiago; Ivonne E Villalobos; Wolfgang Eiermann; Tadeusz Pienkowski; Miguel Martin; Nicholas Robert; John Crown; Valerie Bee; Henry Taupin; Kerry J Flom; Isabelle Tabah-Fisch; Giovanni Pauletti; Mary-Ann Lindsay; Alessandro Riva; Dennis J Slamon Journal: J Clin Oncol Date: 2010-12-28 Impact factor: 44.544
Authors: Johan Staaf; Göran Jönsson; Markus Ringnér; Johan Vallon-Christersson; Dorthe Grabau; Adalgeir Arason; Haukur Gunnarsson; Bjarni A Agnarsson; Per-Olof Malmström; Oskar Th Johannsson; Niklas Loman; Rosa B Barkardottir; Ake Borg Journal: Breast Cancer Res Date: 2010-05-06 Impact factor: 6.466
Authors: Catherine Oakman; Silvia Bessi; Elena Zafarana; Francesca Galardi; Laura Biganzoli; Angelo Di Leo Journal: Breast Cancer Res Date: 2009-04-03 Impact factor: 6.466