Topoisomerase-IIα expression as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel

Virginie Durbecq, Marianne Paesmans, Fatima Cardoso, Christine Desmedt, Angelo Di Leo, Stephen Chan, Kay Friedrichs, Tamas Pinter, Simon Van Belle, Elizabeth Murray, István Bodrogi, Euan Walpole, Bernard Lesperance, Stefan Korec, John Crown, Peter Simmonds, Thimothy J. Perren J., Jean Yves Leroy, Ghizlane Rouas, Christos SotiriouMartine Piccart, Denis Larsimont

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Purpose: The predictive value of topoisomerase-IIα (topo-II) has been evaluated in advanced breast cancer patients randomly treated with single-agent doxorubicin or docetaxel. Experimental design: Primary tumor samples from patients enrolled in a randomized, phase III clinical trial comparing single-agent doxorubicin (75 mg/m2 q3wks) with docetaxel (100 mg/m2 q3wks) were collected and topo-II status was evaluated by immunohistochemistry (clone KiS1). Results: Topo-II status was evaluated in 108 samples, 55 (51%) in the doxorubicin arm and 53 (49%) in the docetaxel arm. An increment of 10% in cells expressing topo-II is associated with a statistically significant odds ratio (OR; 95% confidence interval) of 1.09 (1.03 - 1.15; P = 0.002) for overall response to doxorubicin versus 1.002 (0.94-1.07; P = 0.95) in the docetaxel arm. With increasing topo-II, the favorable OR for overall response to docetaxel compared with doxorubicin decreases to become not significant in patients with topo-II tumor content > 10%. In a multivariate analysis, (a) HER-2 status seems positively correlated with overall response to chemotherapy (OR, 2.34; 95% confidence interval, 0.87-6.27; P = 0.09). (b) Overall response to doxorubicin is significantly lower than overall response to docetaxel (OR, 0.17; 95% confidence interval, 0.04-0.64; P = 0.009) but with a significant interaction term for doxorubicin-treated patients with topo-II tumor content > 10% (OR, 8.31; 95% confidence interval, 1.86-37.03; P = 0.05). Conclusions: (a) Topo-II overexpression confers a higher probability of response in the doxorubicin arm only. (b) Despite being a small retrospective study, this study is in line with previously reported studies and the hypotheses raised are now being tested in a prospective neoadjuvant trial.

Original languageEnglish
Pages (from-to)1207-1214
Number of pages8
JournalMolecular Cancer Therapeutics
Volume3
Issue number10
Publication statusPublished - Oct 2004

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Durbecq, V., Paesmans, M., Cardoso, F., Desmedt, C., Di Leo, A., Chan, S., Friedrichs, K., Pinter, T., Van Belle, S., Murray, E., Bodrogi, I., Walpole, E., Lesperance, B., Korec, S., Crown, J., Simmonds, P., Perren J., T. J., Leroy, J. Y., Rouas, G., ... Larsimont, D. (2004). Topoisomerase-IIα expression as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel. Molecular Cancer Therapeutics, 3(10), 1207-1214.