Changes of topoisomerase IIα expression in breast tumors after neoadjuvant chemotherapy predicts relapse-free survival

Nicola Tinari, Rossano Lattanzio, Clara Natoli, Ettore Cianchetti, Domenico Angelucci, Enrico Ricevuto, Corrado Ficorella, Paolo Marchetti, Saverio Alberti, Mauro Piantelli, Stefano Iacobelli

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Abstract

Purpose: To assess the value of changes in the expression of topoisomerase IIα (TopoII) and the proto-oncogene erbB-2 (HER-2) as predictors of relapse-free survival in women with operable breast cancer treated with anthracycline-based neoadjuvant chemotherapy. Patients and Methods: Seventy-seven patients with primary breast cancer who had undergone neoadjuvant anthracycline-based chemotherapy were included in the present study. TopoII and HER-2 were measured by immunohistochemistry in prechemotherapy and postchemotherapy (at the time of surgery) tumor specimens, and the value of their changes as predictors of relapse-free survival were evaluated by Kaplan-Meier and Cox proportional hazard regression analyses. Results: Neoadjuvant chemotherapy resulted in a significant reduction in the percentage of cells expressing TopoII (P <0.0001). No significant change was observed for HER-2. TopoII and HER-2 expression before chemotherapy predicted tumor response to treatment. Changes in TopoII expression after chemotherapy were strongly associated with a poor relapse-free survival (P <0.0001) in a Cox multivariate analysis adjusted for other clinicopathologic prognostic factors. Conclusion: Changes in TopoII expression after anthracycline-based neoadjuvant chemotherapy is an independent predictor of a poor relapse-free survival in patients with breast cancer. Tumor cells displaying an increased TopoII expression after treatment may be responsible for relapses, and may, therefore, define a group of patients with anthracycline-resistant breast cancer.

Original languageEnglish
Pages (from-to)1501-1506
Number of pages6
JournalClinical Cancer Research
Volume12
Issue number5
DOIs
Publication statusPublished - Mar 1 2006

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Type II DNA Topoisomerase
Breast Neoplasms
Anthracyclines
Recurrence
Drug Therapy
Survival
Neoplasms
Proto-Oncogenes
Multivariate Analysis
Immunohistochemistry
Regression Analysis
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tinari, N., Lattanzio, R., Natoli, C., Cianchetti, E., Angelucci, D., Ricevuto, E., ... Iacobelli, S. (2006). Changes of topoisomerase IIα expression in breast tumors after neoadjuvant chemotherapy predicts relapse-free survival. Clinical Cancer Research, 12(5), 1501-1506. https://doi.org/10.1158/1078-0432.CCR-05-0978

Changes of topoisomerase IIα expression in breast tumors after neoadjuvant chemotherapy predicts relapse-free survival. / Tinari, Nicola; Lattanzio, Rossano; Natoli, Clara; Cianchetti, Ettore; Angelucci, Domenico; Ricevuto, Enrico; Ficorella, Corrado; Marchetti, Paolo; Alberti, Saverio; Piantelli, Mauro; Iacobelli, Stefano.

In: Clinical Cancer Research, Vol. 12, No. 5, 01.03.2006, p. 1501-1506.

Research output: Contribution to journalArticle

Tinari, N, Lattanzio, R, Natoli, C, Cianchetti, E, Angelucci, D, Ricevuto, E, Ficorella, C, Marchetti, P, Alberti, S, Piantelli, M & Iacobelli, S 2006, 'Changes of topoisomerase IIα expression in breast tumors after neoadjuvant chemotherapy predicts relapse-free survival', Clinical Cancer Research, vol. 12, no. 5, pp. 1501-1506. https://doi.org/10.1158/1078-0432.CCR-05-0978
Tinari, Nicola ; Lattanzio, Rossano ; Natoli, Clara ; Cianchetti, Ettore ; Angelucci, Domenico ; Ricevuto, Enrico ; Ficorella, Corrado ; Marchetti, Paolo ; Alberti, Saverio ; Piantelli, Mauro ; Iacobelli, Stefano. / Changes of topoisomerase IIα expression in breast tumors after neoadjuvant chemotherapy predicts relapse-free survival. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 5. pp. 1501-1506.
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AU - Lattanzio, Rossano

AU - Natoli, Clara

AU - Cianchetti, Ettore

AU - Angelucci, Domenico

AU - Ricevuto, Enrico

AU - Ficorella, Corrado

AU - Marchetti, Paolo

AU - Alberti, Saverio

AU - Piantelli, Mauro

AU - Iacobelli, Stefano

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N2 - Purpose: To assess the value of changes in the expression of topoisomerase IIα (TopoII) and the proto-oncogene erbB-2 (HER-2) as predictors of relapse-free survival in women with operable breast cancer treated with anthracycline-based neoadjuvant chemotherapy. Patients and Methods: Seventy-seven patients with primary breast cancer who had undergone neoadjuvant anthracycline-based chemotherapy were included in the present study. TopoII and HER-2 were measured by immunohistochemistry in prechemotherapy and postchemotherapy (at the time of surgery) tumor specimens, and the value of their changes as predictors of relapse-free survival were evaluated by Kaplan-Meier and Cox proportional hazard regression analyses. Results: Neoadjuvant chemotherapy resulted in a significant reduction in the percentage of cells expressing TopoII (P <0.0001). No significant change was observed for HER-2. TopoII and HER-2 expression before chemotherapy predicted tumor response to treatment. Changes in TopoII expression after chemotherapy were strongly associated with a poor relapse-free survival (P <0.0001) in a Cox multivariate analysis adjusted for other clinicopathologic prognostic factors. Conclusion: Changes in TopoII expression after anthracycline-based neoadjuvant chemotherapy is an independent predictor of a poor relapse-free survival in patients with breast cancer. Tumor cells displaying an increased TopoII expression after treatment may be responsible for relapses, and may, therefore, define a group of patients with anthracycline-resistant breast cancer.

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