Amplification and overexpression of topoisomerase IIα predict response to anthracycline-based therapy in locally advanced breast cancer

John S. Coon, Elizabeth Marcus, Shalina Gupta-Burt, Steven Seelig, Kris Jacobson, Shande Chen, Vivian Renta, Geraldo Fronda, Harvey D. Preisler

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173 Scopus citations

Abstract

Purpose: The putative association between erbB-2 overexpression and favorable response to anthracyline-based therapy in breast cancer is controversial, and the mechanism unclear. We sought to determine whether coamplification and overexpression of the topoisomerase IIα gene, near erbB-2 on chromosome 17, and a known anthracycline target, may underlie the association. Experimental Design: Thirty-five patients who had locally advanced breast cancer (LABC) and who had received neoadjuvant, anthracycline-based therapy were studied. Copy number of topoisomerase IIα and erbB-2 was determined by fluorescence in situ hybridization, and expression by immunohistochemistry. Results: Of 8 patients with erbB-2 amplification, 5 had a complete response (CR) or minimal residual disease (MRD), 3 had a partial response (PR), and none had stable (StD) or progressive disease (PD) at the time of mastectomy, versus 3 CR or MRD, 16 PR, and 8 StD or PD for patients without amplification (P = 0.008). In contrast, erbB-2 overexpression was not significantly associated with response (P = 0.114). Of 6 patients with topoisomerase IIα amplification, 4 had CR or MRD, 2 PR, and none StD or PD, versus 4 CR or MRD, 17 PR, and 8 StD or PD for patients without amplification (P = 0.034). All of the tumors with topoisomerase IIα amplification also had erbB-2 amplification, but not vice versa. Overexpression of topoisomerase IIα (9 patients) was also associated with favorable response (P = 0.021). Conclusions: Coamplification of erbB-2 and topoisomerase IIα is significantly associated with favorable local response to anthracycline-based therapy in LABC. The expression data favor a plausible mechanism based on topoisomerase IIα biology.

Original languageEnglish
Pages (from-to)1061-1067
Number of pages7
JournalClinical Cancer Research
Volume8
Issue number4
StatePublished - 1 Apr 2002

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    Coon, J. S., Marcus, E., Gupta-Burt, S., Seelig, S., Jacobson, K., Chen, S., Renta, V., Fronda, G., & Preisler, H. D. (2002). Amplification and overexpression of topoisomerase IIα predict response to anthracycline-based therapy in locally advanced breast cancer. Clinical Cancer Research, 8(4), 1061-1067.