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

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Abstract

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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Authors and Affiliations

  1. The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, Fulham Road, London, SW3 6JB, UK

    Edurne Arriola, Socorro Maria Rodriguez-Pinilla, Maryou B. K. Lambros, Michelle James, Kay Savage, Mitch Dowsett & Jorge S. Reis-Filho

  2. Department of Academic Biochemistry, Royal Marsden Hospital, London, SW3 6JJ, UK

    Edurne Arriola, Robin L. Jones & Mitch Dowsett

  3. Breast Unit, Royal Marsden Hospital, London, SW3 6JJ, UK

    Ian E. Smith

Authors
  1. Edurne Arriola
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  2. Socorro Maria Rodriguez-Pinilla
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  3. Maryou B. K. Lambros
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  4. Robin L. Jones
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  5. Michelle James
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  6. Kay Savage
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  7. Ian E. Smith
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  8. Mitch Dowsett
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  9. Jorge S. Reis-Filho
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Correspondence to Jorge S. Reis-Filho.

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Arriola, E., Rodriguez-Pinilla, S.M., Lambros, M.B.K. et al. Topoisomerase II alpha amplification may predict benefit from adjuvant anthracyclines in HER2 positive early breast cancer. Breast Cancer Res Treat 106, 181–189 (2007). https://doi.org/10.1007/s10549-006-9492-5

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  • DOI: https://doi.org/10.1007/s10549-006-9492-5

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