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Amplification and overexpression of topoisomerase IIalpha predict response to anthracycline-based therapy in locally advanced breast cancer.
Clin Cancer Res. 2002 Apr; 8(4):1061-7.CC

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 IIalpha 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 IIalpha 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 IIalpha 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 IIalpha amplification also had erbB-2 amplification, but not vice versa. Overexpression of topoisomerase IIalpha (9 patients) was also associated with favorable response (P = 0.021).

CONCLUSIONS

Coamplification of erbB-2 and topoisomerase IIalpha is significantly associated with favorable local response to anthracycline-based therapy in LABC. The expression data favor a plausible mechanism based on topoisomerase IIalpha biology.

Authors+Show Affiliations

Rush Medical College, Chicago, Illinois 60612, USA. jcoon@rush.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11948114

Citation

Coon, John S., et al. "Amplification and Overexpression of Topoisomerase IIalpha Predict Response to Anthracycline-based Therapy in Locally Advanced Breast Cancer." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 8, no. 4, 2002, pp. 1061-7.
Coon JS, Marcus E, Gupta-Burt S, et al. Amplification and overexpression of topoisomerase IIalpha predict response to anthracycline-based therapy in locally advanced breast cancer. Clin Cancer Res. 2002;8(4):1061-7.
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 IIalpha predict response to anthracycline-based therapy in locally advanced breast cancer. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 8(4), 1061-7.
Coon JS, et al. Amplification and Overexpression of Topoisomerase IIalpha Predict Response to Anthracycline-based Therapy in Locally Advanced Breast Cancer. Clin Cancer Res. 2002;8(4):1061-7. PubMed PMID: 11948114.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amplification and overexpression of topoisomerase IIalpha predict response to anthracycline-based therapy in locally advanced breast cancer. AU - Coon,John S, AU - Marcus,Elizabeth, AU - Gupta-Burt,Shalina, AU - Seelig,Steven, AU - Jacobson,Kris, AU - Chen,Shande, AU - Renta,Vivian, AU - Fronda,Geraldo, AU - Preisler,Harvey D, PY - 2002/4/12/pubmed PY - 2002/8/13/medline PY - 2002/4/12/entrez SP - 1061 EP - 7 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 8 IS - 4 N2 - 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 IIalpha 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 IIalpha 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 IIalpha 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 IIalpha amplification also had erbB-2 amplification, but not vice versa. Overexpression of topoisomerase IIalpha (9 patients) was also associated with favorable response (P = 0.021). CONCLUSIONS: Coamplification of erbB-2 and topoisomerase IIalpha is significantly associated with favorable local response to anthracycline-based therapy in LABC. The expression data favor a plausible mechanism based on topoisomerase IIalpha biology. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/11948114/Amplification_and_overexpression_of_topoisomerase_IIalpha_predict_response_to_anthracycline_based_therapy_in_locally_advanced_breast_cancer_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11948114 DB - PRIME DP - Unbound Medicine ER -