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Molecular Cancer Therapeutics
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Research Articles: Therapeutics, Targets, and Development

Gene expression profiles do not consistently predict the clinical treatment response in locally advanced breast cancer

Therese Sørlie, Charles M. Perou, Cheng Fan, Stephanie Geisler, Turid Aas, Andrew Nobel, Gun Anker, Lars A. Akslen, David Botstein, Anne-Lise Børresen-Dale and Per Eystein Lønning
Therese Sørlie
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Charles M. Perou
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Cheng Fan
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Stephanie Geisler
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Turid Aas
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Andrew Nobel
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Gun Anker
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Lars A. Akslen
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David Botstein
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Anne-Lise Børresen-Dale
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Per Eystein Lønning
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DOI: 10.1158/1535-7163.MCT-06-0126 Published November 2006
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Abstract

Neoadjuvant treatment offers an opportunity to correlate molecular variables to treatment response and to explore mechanisms of drug resistance in vivo. Here, we present a statistical analysis of large-scale gene expression patterns and their relationship to response following neoadjuvant chemotherapy in locally advanced breast cancers. We analyzed cDNA expression data from 81 tumors from two patient series, one treated with doxorubicin alone (51) and the other treated with 5-fluorouracil and mitomycin (30), and both were previously studied for correlations between TP53 status and response to therapy. We observed a low frequency of progressive disease within the luminal A subtype from both series (2 of 36 versus 13 of 45 patients; P = 0.0089) and a high frequency of progressive disease among patients with luminal B type tumors treated with doxorubicin (5 of 8 patients; P = 0.0078); however, aside from these two observations, no other consistent associations between response to chemotherapy and tumor subtype were observed. These specific associations could possibly be explained by covariance with TP53 mutation status, which also correlated with tumor subtype. Using supervised analysis, we could not uncover a gene profile that could reliably (>70% accuracy and specificity) predict response to either treatment regimen. [Mol Cancer Ther 2006;5(11):2914–8]

Keywords:
  • Prediction
  • breast cancer
  • expression profiling
  • molecular subtypes

Footnotes

  • ↵8 Supplementary material for this article is available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

  • ↵9 http://www.microarray.org/sfgf/jsp/home.

  • ↵10 http://genome-www.stanford.edu/breast_cancer/.

  • Grant support: Norwegian Cancer Society, Norwegian Research Council, “SalusAnsvar” Award (A-L. Børresen-Dale), National Cancer Institute Breast Specialized Program of Research Excellence program grant P50-CA58223-09A1, and Breast Cancer Research Foundation (C.M. Perou).

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • Note: The analyses of the data presented in this report are original work of the authors and have not been presented previously. Some molecular data on these cases have been used in two previous studies (see refs. 3 and 4), and the raw microarray data have been published in a different context (see ref. 9).

    • Accepted September 25, 2006.
    • Received March 7, 2006.
    • Revision received June 4, 2006.
  • American Association for Cancer Research
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Molecular Cancer Therapeutics: 5 (11)
November 2006
Volume 5, Issue 11
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Gene expression profiles do not consistently predict the clinical treatment response in locally advanced breast cancer
Therese Sørlie, Charles M. Perou, Cheng Fan, Stephanie Geisler, Turid Aas, Andrew Nobel, Gun Anker, Lars A. Akslen, David Botstein, Anne-Lise Børresen-Dale and Per Eystein Lønning
Mol Cancer Ther November 1 2006 (5) (11) 2914-2918; DOI: 10.1158/1535-7163.MCT-06-0126

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Gene expression profiles do not consistently predict the clinical treatment response in locally advanced breast cancer
Therese Sørlie, Charles M. Perou, Cheng Fan, Stephanie Geisler, Turid Aas, Andrew Nobel, Gun Anker, Lars A. Akslen, David Botstein, Anne-Lise Børresen-Dale and Per Eystein Lønning
Mol Cancer Ther November 1 2006 (5) (11) 2914-2918; DOI: 10.1158/1535-7163.MCT-06-0126
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Molecular Cancer Therapeutics
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