Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer

被引:101
作者
Arriola, Edurne
Rodriguez-Pinilla, Socorro Maria
Lambros, Maryou B. K.
Jones, Robin L.
James, Michelle
Savage, Kay
Smith, Ian E.
Dowsett, Mitch
Reis-Filho, Jorge S.
机构
[1] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England
[2] Royal Marsden Hosp, Dept Acad Biochem, London SW3 6JJ, England
[3] Royal Marsden Hosp, Breast Unit, London SW3 6JJ, England
关键词
anthracyclines; breast cancer; chromogenic in situ hubridisation; HER2; topoisomerase II alpha;
D O I
10.1007/s10549-006-9492-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background TOP2A gene encodes topoisomerase II alpha, the direct molecular target of anthracyclines. This gene is frequently coamplified with HER2. The aims of this study were to analyse the pattern of TOP2A amplification and protein expression in relation to the molecular subgroups of breast cancers; and to define the impact of TOP2A amplification on the outcome of a series of patients homogeneously treated with adjuvant anthracyclines. Methods A cohort of 245 patients with early breast cancer homogeneously treated with anthracyclines in the adjuvant setting was selected. A tissue microarray containing these cancers was used to determine HER2 and TOP2A gene copy number by means of chromogenic in situ hybridization. Immunohistochemical staining of topoisomerase II alpha was also performed using a monoclonal antibody (Ki-S1). TOP2A amplification and protein expression were correlated with classical prognostic parameters, expression of immunohistochemical markers and with a gene expression profiling classification using surrogate immunohistochemical markers. Kaplan-Meier method was used to construct survival curves and results were compared with log-rank test. Results TOP2A amplification was restricted to tumours with HER2 amplification and was significantly associated with ER positivity. In the subgroup of patients with HER2 amplified tumours, TOP2A amplification predicted a better overall survival and disease free survival (P = 0.028 and 0.026, respectively). On multivariate analysis, TOP2A amplification maintained its predictive value for DFS. Conclusion TOP2A amplification is likely to be a useful marker to predict the subset of patients who will benefit from anthracyclines.
引用
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页码:181 / 189
页数:9
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