Research article
Evaluation of biological pathways involved in chemotherapy response in breast cancer
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* Corresponding author: Lajos Pusztai lpusztai@mdanderson.org
1 Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
2 Departments of Bioinformatics and Computation Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
3 Department of Pathology of The University of Texas M. D. Anderson Cancer Center, Houston, TX
4 Department of Molecular Diagnostics, National Medical Center, Budapest, Hungary
5 Unit UPRES03535, Institut Gustave Roussy, Villejuif, France
6 Jules Bordet Institut, Brussels, Belgium
Breast Cancer Research 2008, 10:R37 doi:10.1186/bcr2088
Published: 29 April 2008Abstract
Introduction
Our goal was to examine the association between biological pathways and response to chemotherapy in estrogen receptor (ER)-positive and ER-negative breast cancers separately.
Methods
Gene set enrichment analysis including 852 predefined gene sets, was applied to gene expression data from 51 ER-negative and 82 ER-positive breast cancers that were all treated with a preoperative paclitaxel, 5-fluoruracil, doxorubicin and cyclophosphamide chemotherapy.
Results
Twenty-seven (53%) ER-negative and 7 (9%) ER-positive patients had pathologic complete response (pCR) to therapy. Among the ER-negative cancers, a proliferation gene signature (FDR q = 0.1), the Genomic Grade Index (FDR q = 0.044) and the E2F3 pathway (FDR q = 0.22, p = 0.07) signature were enriched in the pCR group. Among the ER-positive cancers, the proliferation signature (FDR q = 0.001) and the Genomic Grade Index (FDR q = 0.015) were also significantly enriched in cases with pCR. Ki67 expression, as single gene marker of proliferation, did not provide the same information as the entire proliferation signature. An ER-associated gene set (FDR q = 0.03) and a mutant p53-gene signature (FDR q = 0.0019) were enriched in ER-positive cancers with residual cancer.
Conclusion
Proliferation- and genomic grade-related gene signatures are associated with chemotherapy sensitivity in both ER-negative and -positive breast cancers. Genes involved in the E2F3 pathway are associated with chemotherapy sensitivity among ER-negative cancers. The mutant p53-signature and expression of ER-related genes were associated with lower sensitivity to chemotherapy in ER-positive breast cancers only.