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Carbonic anhydrase IX is a predictive marker of doxorubicin resistance in early-stage breast cancer independent of HER2 and TOP2A amplification.

Publication ,  Journal Article
Betof, AS; Rabbani, ZN; Hardee, ME; Kim, SJ; Broadwater, G; Bentley, RC; Snyder, SA; Vujaskovic, Z; Oosterwijk, E; Harris, LN; Horton, JK ...
Published in: Br J Cancer
February 28, 2012

BACKGROUND: In early-stage breast cancer, adjuvant chemotherapy is associated with significant systemic toxicity with only a modest survival benefit. Therefore, there is considerable interest in identifying predictive markers of response to therapy. Doxorubicin, one of the most common drugs used to treat breast cancer, is an anthracycline chemotherapeutic agent, a class of drugs known to be affected by hypoxia. Accordingly, we examined whether expression of the endogenous hypoxia marker carbonic anhydrase IX (CA IX) is predictive of outcome in early-stage breast cancer patients treated with doxorubicin. METHODS: We obtained 209 early-stage pre-treatment surgically-resected breast tumours from patients, who received doxorubicin in their chemotherapeutic regimen and had >10 years of follow-up. Immunohistochemistry was used to detect CA IX, and we used fluorescence in situ hybridisation to detect both human epidermal growth factor receptor (HER2) and DNA topoisomerase II-alpha (TOP2A) gene amplification. RESULTS: Carbonic anhydrase IX intensity was significantly correlated with progression-free survival (PFS) and overall survival (OS) in patients receiving 300 mg m(-2) of doxorubicin (HR=1.82 and 3.77; P=0.0014 and 0.010, respectively). There was a significant, inverse correlation between CA IX score and oestrogen receptor expression, but no significant correlations were seen with either HER2 or TOP2A ratio. CONCLUSION: We demonstrate that CA IX expression is correlated with worse PFS and OS for breast cancer patients treated with doxorubicin, independent of HER2 or TOP2A gene amplification. This study provides evidence that using CA IX to detect hypoxia in surgically-resected breast tumours may be of clinical use in choosing an appropriate chemotherapy regimen.

Duke Scholars

Published In

Br J Cancer

DOI

EISSN

1532-1827

Publication Date

February 28, 2012

Volume

106

Issue

5

Start / End Page

916 / 922

Location

England

Related Subject Headings

  • Poly-ADP-Ribose Binding Proteins
  • Oncology & Carcinogenesis
  • Middle Aged
  • Humans
  • Genes, erbB-2
  • Gene Amplification
  • Female
  • Drug Resistance, Neoplasm
  • Doxorubicin
  • Disease-Free Survival
 

Citation

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Betof, A. S., Rabbani, Z. N., Hardee, M. E., Kim, S. J., Broadwater, G., Bentley, R. C., … Blackwell, K. L. (2012). Carbonic anhydrase IX is a predictive marker of doxorubicin resistance in early-stage breast cancer independent of HER2 and TOP2A amplification. Br J Cancer, 106(5), 916–922. https://doi.org/10.1038/bjc.2012.32
Betof, A. S., Z. N. Rabbani, M. E. Hardee, S. J. Kim, G. Broadwater, R. C. Bentley, S. A. Snyder, et al. “Carbonic anhydrase IX is a predictive marker of doxorubicin resistance in early-stage breast cancer independent of HER2 and TOP2A amplification.Br J Cancer 106, no. 5 (February 28, 2012): 916–22. https://doi.org/10.1038/bjc.2012.32.
Betof AS, Rabbani ZN, Hardee ME, Kim SJ, Broadwater G, Bentley RC, et al. Carbonic anhydrase IX is a predictive marker of doxorubicin resistance in early-stage breast cancer independent of HER2 and TOP2A amplification. Br J Cancer. 2012 Feb 28;106(5):916–22.
Betof, A. S., et al. “Carbonic anhydrase IX is a predictive marker of doxorubicin resistance in early-stage breast cancer independent of HER2 and TOP2A amplification.Br J Cancer, vol. 106, no. 5, Feb. 2012, pp. 916–22. Pubmed, doi:10.1038/bjc.2012.32.
Betof AS, Rabbani ZN, Hardee ME, Kim SJ, Broadwater G, Bentley RC, Snyder SA, Vujaskovic Z, Oosterwijk E, Harris LN, Horton JK, Dewhirst MW, Blackwell KL. Carbonic anhydrase IX is a predictive marker of doxorubicin resistance in early-stage breast cancer independent of HER2 and TOP2A amplification. Br J Cancer. 2012 Feb 28;106(5):916–922.

Published In

Br J Cancer

DOI

EISSN

1532-1827

Publication Date

February 28, 2012

Volume

106

Issue

5

Start / End Page

916 / 922

Location

England

Related Subject Headings

  • Poly-ADP-Ribose Binding Proteins
  • Oncology & Carcinogenesis
  • Middle Aged
  • Humans
  • Genes, erbB-2
  • Gene Amplification
  • Female
  • Drug Resistance, Neoplasm
  • Doxorubicin
  • Disease-Free Survival