uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
TOP2A and HER2 gene amplification as predictors of response to anthracycline treatment in breast cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Show others and affiliations
2006 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 45, no 5, 590-596 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of this study was to evaluate amplification of topoisomerase IIalpha (TOP2A) and HER2 genes as predictors of response to chemotherapy in advanced breast cancer. Gene copy number of TOP2A and HER2 were analysed with chromogenic in situ hybridization (CISH) on paraffin-embedded tissue sections from the primary tumour of 85 patients treated with anthracycline containing chemotherapy. TOP2A gene amplification was present in 14 (16%) and HER2 gene amplification in 38 (45%) of the primary tumours. Two of the 14 cases with TOP2A amplification were amplified without concurrent HER2 amplification. Neither TOP2A nor HER2 gene amplification were significantly associated with response to chemotherapy (p = 0.35 and p = 0.49, respectively).

Place, publisher, year, edition, pages
2006. Vol. 45, no 5, 590-596 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-95411DOI: 10.1080/02841860500543182OAI: oai:DiVA.org:uu-95411DiVA: diva2:169605
Available from: 2007-02-02 Created: 2007-02-02 Last updated: 2011-11-03Bibliographically approved
In thesis
1. Chemosensitivity in Breast Cancer
Open this publication in new window or tab >>Chemosensitivity in Breast Cancer
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Breast cancer mortality in Sweden is now in decline, thanks to early detection and the wide use of adjuvant endocrine therapy and chemotherapy.

While hormone receptor status is predictive of response to endocrine treatment, there is no clinically useful predictive marker of a patient’s response to chemotherapy. Consequently, patients receive chemotherapy with considerable toxicity but minimal benefit. The aim of this thesis was to investigate a number of methods with the potential to predict response to chemotherapy and thus enhance treatment efficacy in breast cancer patients.

We found that topo IIα, the key target enzyme of topo II inhibitors, is significantly expressed in nonproliferating breast cancer cells. This finding may explain why topo II inhibitors are effective in patients with slow growing tumors and a low proliferation rate.

Topo IIα gene amplification was suggestive of increased response to anthracyclines in advanced breast cancer, whereas the oncogene HER2 had no predictive value by itself. These findings are in accordance with current knowledge.

Cyclin A, a marker of cell proliferation, showed good prognostic value but did not predict response to chemotherapy in advanced breast cancer.

In vitro chemosensitivity testing with FMCA predicted tumor response in patients with advanced breast cancer with a sensitivity of 89% and a specificity of 53%. Our results are consistent with the results from similar assays, which predict drug resistance with good accuracy while clinical drug sensitivity is less reliably predicted. The use of FMCA and similar assays is not yet recommended outside clinical trials; their main utility is in preclinical testing of new anti-cancer drugs, including targeted therapies.

The combination of epirubicin, capecitabine, and cisplatin (EXC) demonstrated high clinical response rate (74%) and pathological complete response rate (22%) in locally advanced breast cancer, but with cumbersome toxicity. The fluoropyrimidine biomarkers TS, TP, and DPD did not predict response to the EXC regimen.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 83 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 221
Oncology, breast cancer, chemotherapy, anthracycline, predictive, topoisomerase, TOP2A, HER2, cyclin A, in vitro, Onkologi
urn:nbn:se:uu:diva-7459 (URN)978-91-554-6787-6 (ISBN)
Public defence
2007-02-23, Wilandersalen, M-huset, Universitetssjukhuset, Örebro, 13:15
Available from: 2007-02-02 Created: 2007-02-02Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Villman, Kenneth
By organisation
Department of Oncology, Radiology and Clinical Immunology
In the same journal
Acta Oncologica
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 206 hits
ReferencesLink to record
Permanent link

Direct link