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Changes of Topoisomerase II Expression in Breast Tumors after Neoadjuvant Chemotherapy Predicts Relapse-Free Survival

Authors' Affiliations: ¹ "G. D'Annunzio" University Foundation and Department of Oncology and Neurosciences, University G. D'Annunzio Medical School, Chieti and ² Department of Medical Oncology, University of L'Aquila, L'Aquila, Italy

Requests for reprints: Stefano Iacobelli, Department of Oncology and Neurosciences, Section of Medical Oncology, University "G. D'Annunzio" Medical School, 66013 Chieti, Italy. Phone: 39-871-355-6732; Fax: 39-871-355-6707; E-mail: iacobell{at}unich.it.

Purpose: To assess the value of changes in the expression of topoisomerase II (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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				C. Shimizu, M. Ando, T. Kouno, N. Katsumata, and Y. Fujiwara Current Trends and Controversies over Pre-operative Chemotherapy for Women with Operable Breast Cancer Jpn. J. Clin. Oncol., January 3, 2007; (2007) hyl122v1. [Abstract] [Full Text] [PDF]