PURPOSE: Amplification and deletion of the TOP2A gene have been reported as positive predictive markers of response to anthracycline-based therapy. We determined the status of the HER2 and TOP2A genes in a large cohort of breast cancer patients treated with adjuvant doxorubicin (A) and cyclophosphamide (C). PATIENTS AND METHODS: TOP2A/CEP17 and HER2/CEP17 fluorescent in situ hybridization (FISH) were performed on tissue microarrays (TMAs) constructed from 2,123 of the 3,125 women with moderate-risk primary breast cancer who received equivalent doses of either concurrent adjuvant chemotherapy with A plus C (n = 1,592) or sequential A followed by C (n = 1,533). RESULTS: An abnormal TOP2A genotype was identified for 153 (9.4%) of 1,626 patients (4.0% amplified; 5.4% deleted). An abnormal HER2 genotype was identified for 303 (20.4%) of 1,483 patients (18.8% amplified; 1.6% deleted). No significant differences in either overall survival (OS) or disease-free survival (DFS) were identified for TOP2A. In univariate analysis, OS and DFS rates were strongly and adversely associated only with higher levels of HER2 amplification (ratio > or = 4.0). Survival was not associated with low-level HER2 amplification (ratio > or = 2; OS hazard ratio [HR], 1.14; P = .39; DFS HR, 1.07; P = .62), but it was associated for a ratio > or = 4 (OS HR, 1.45; P = .03; DFS HR, 1.38; P = .033), in which analysis was adjusted for menopausal status, hormone receptor status, treatment, number of positive nodes, and tumor size. CONCLUSION: In this population of patients with early-stage breast cancer who were treated with adjuvant AC chemotherapy, TOP2A abnormalities were not associated with outcome. HER2 high-level amplification was a prognostic marker in anthracycline-treated patients.
PURPOSE: Amplification and deletion of the TOP2A gene have been reported as positive predictive markers of response to anthracycline-based therapy. We determined the status of the HER2 and TOP2A genes in a large cohort of breast cancerpatients treated with adjuvant doxorubicin (A) and cyclophosphamide (C). PATIENTS AND METHODS: TOP2A/CEP17 and HER2/CEP17 fluorescent in situ hybridization (FISH) were performed on tissue microarrays (TMAs) constructed from 2,123 of the 3,125 women with moderate-risk primary breast cancer who received equivalent doses of either concurrent adjuvant chemotherapy with A plus C (n = 1,592) or sequential A followed by C (n = 1,533). RESULTS: An abnormal TOP2A genotype was identified for 153 (9.4%) of 1,626 patients (4.0% amplified; 5.4% deleted). An abnormal HER2 genotype was identified for 303 (20.4%) of 1,483 patients (18.8% amplified; 1.6% deleted). No significant differences in either overall survival (OS) or disease-free survival (DFS) were identified for TOP2A. In univariate analysis, OS and DFS rates were strongly and adversely associated only with higher levels of HER2 amplification (ratio > or = 4.0). Survival was not associated with low-level HER2 amplification (ratio > or = 2; OS hazard ratio [HR], 1.14; P = .39; DFS HR, 1.07; P = .62), but it was associated for a ratio > or = 4 (OS HR, 1.45; P = .03; DFS HR, 1.38; P = .033), in which analysis was adjusted for menopausal status, hormone receptor status, treatment, number of positive nodes, and tumor size. CONCLUSION: In this population of patients with early-stage breast cancer who were treated with adjuvant AC chemotherapy, TOP2A abnormalities were not associated with outcome. HER2 high-level amplification was a prognostic marker in anthracycline-treated patients.
Authors: Minna Tanner; Jorma Isola; Tom Wiklund; Björn Erikstein; Pirkko Kellokumpu-Lehtinen; Per Malmström; Nils Wilking; Jonas Nilsson; Jonas Bergh Journal: J Clin Oncol Date: 2006-05-08 Impact factor: 44.544
Authors: Peggy L Porter; William E Barlow; I-Tien Yeh; Ming Gang Lin; Xiaopu P Yuan; Elizabeth Donato; George W Sledge; Charles L Shapiro; James N Ingle; Charles M Haskell; Kathy S Albain; James M Roberts; Robert B Livingston; Daniel F Hayes Journal: J Natl Cancer Inst Date: 2006-12-06 Impact factor: 13.506
Authors: Kathleen I Pritchard; Lois E Shepherd; Frances P O'Malley; Irene L Andrulis; Dongsheng Tu; Vivien H Bramwell; Mark N Levine Journal: N Engl J Med Date: 2006-05-18 Impact factor: 91.245
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 Journal: J Clin Oncol Date: 2005-10-20 Impact factor: 44.544
Authors: Lisa M McShane; Douglas G Altman; Willi Sauerbrei; Sheila E Taube; Massimo Gion; Gary M Clark Journal: J Natl Cancer Inst Date: 2005-08-17 Impact factor: 13.506
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: Katrín A Gunnarsdóttir; Maj-Britt Jensen; David Zahrieh; Richard D Gelber; Ann Knoop; Marco Bonetti; Henning Mouridsen; Bent Ejlertsen Journal: Breast Cancer Res Treat Date: 2010-05-13 Impact factor: 4.872
Authors: Malini Harigopal; William E Barlow; Greg Tedeschi; Peggy L Porter; I-Tien Yeh; Charles Haskell; Robert Livingston; Gabriel N Hortobagyi; George Sledge; Charles Shapiro; James N Ingle; David L Rimm; Daniel F Hayes Journal: Am J Pathol Date: 2010-02-11 Impact factor: 4.307
Authors: Christian Schindlbeck; D Mayr; C Olivier; B Rack; V Engelstaedter; J Jueckstock; C Jenderek; U Andergassen; U Jeschke; K Friese Journal: J Cancer Res Clin Oncol Date: 2010-01-06 Impact factor: 4.553
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: Maria Unni Rømer; Sune Boris Nygård; Ib Jarle Christensen; Signe Lykke Nielsen; Kirsten Vang Nielsen; Sven Müller; David Hersi Smith; Ben Vainer; Hans Jørgen Nielsen; Nils Brünner Journal: Mol Oncol Date: 2012-10-11 Impact factor: 6.603