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Title:
Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer | Breast Cancer Research and Treatment
Description:
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.
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cancer, breast, article, google, scholar, cas, pubmed, topoisomerase, amplification, predictive, iialpha, adjuvant, expression, patients, alpha, topa, gene, clin, chemotherapy, early, molecular, oncol, response, res, research, anthracyclines, treated, situ, prognostic, pathol, doxorubicin, reisfilho, markers, primary, cyclophosphamide, privacy, cookies, content, arriola, lambros, protein, cancers, chromogenic, hybridization, immunohistochemical, access, med, therapy, receptor, fluorouracil,
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month download article/chapter axillary lymph node-positive node-negative tumors 2 cm topoisomerase-ii alpha expression early breast cancer socorro maria rodriguez-pinilla reis-filho department neoadjuvant anthracycline-based chemotherapy primary anthracycline-based chemotherapy 2/neu-amplified breast cancer related subjects patients homogeneously treated topoisomerase ii alpha topoisomerase ii-alpha breast cancer treatment full article pdf direct molecular target operable breast cancer breast cancer staging reis-filho eukaryotic topoisomerase ii privacy choices/manage cookies metastatic breast cancer human breast cancer kellokumpu-lehtinen pl dna topoisomerase ii gene expression patterns breast tumor subtypes topoisomerase iialpha expression topoisomerase iialpha associate mitch dowsett & jorge invasive breast carcinoma anthracycline-based therapy topoisomerase iia amplifications article arriola malignant breast tissue di leo tissue-based detection growth fraction determination topo-isomerase iialpha cancer research molecular genetic studies european economic area pierga jy thor ad long-term follow unlocking pathology archives royal marsden hospital top2a amplification predicted top2a amplification maintained
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- Brenton JD, Carey LA, Ahmed AA et al (2005) Molecular classification and molecular forecasting of breast cancer: ready for clinical application?
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headline:Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer
description: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. 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. 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. TOP2A amplification is likely to be a useful marker to predict the subset of patients who will benefit from anthracyclines.
datePublished:2007-01-27T00:00:00Z
dateModified:2007-01-27T00:00:00Z
pageStart:181
pageEnd:189
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Anthracyclines
Breast cancer
Chromogenic in situ hubridisation
HER2
Topoisomerase II alpha
Oncology
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headline:Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer
description: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. 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. 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. TOP2A amplification is likely to be a useful marker to predict the subset of patients who will benefit from anthracyclines.
datePublished:2007-01-27T00:00:00Z
dateModified:2007-01-27T00:00:00Z
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Anthracyclines
Breast cancer
Chromogenic in situ hubridisation
HER2
Topoisomerase II alpha
Oncology
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