Evaluation of biological pathways involved in chemotherapy response in breast cancer

Attila Tordai, Jing Wang, Fabrice Andre, Cornelia Liedtke, Kai Yan, Christos Sotiriou, Gabriel N. Hortobagyi, W. Fraser Symmans, Lajos Pusztai

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Abstract

Introduction: Our goal was to examine the association between biological pathways and response to chemotherapy in estrogen receptor-positive (ER+) and ER-negative (ER-) breast tumors separately.Methods: Gene set enrichment analysis including 852 predefined gene sets was applied to gene expression data from 51 ER- and 82 ER+ breast tumors that were all treated with a preoperative paclitaxel, 5-fluoruracil, doxorubicin, and cyclophosphamide chemotherapy.Results: Twenty-seven (53%) ER- and 7 (9%) ER+ patients had pathologic complete response (pCR) to therapy. Among the ER- tumors, a proliferation gene signature (false discovery rate [FDR] q = 0.1), the genomic grade index (FDR q = 0.044), and the E2F3 pathway signature (FDR q = 0.22, P = 0.07) were enriched in the pCR group. Among the ER+ tumors, 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+ tumors with residual cancer.Conclusion: Proliferation- and genomic grade-related gene signatures are associated with chemotherapy sensitivity in both ER- and ER+ breast tumors. Genes involved in the E2F3 pathway are associated with chemotherapy sensitivity among ER- tumors. The mutant p53 signature and expression of ER-related genes were associated with lower sensitivity to chemotherapy in ER+ breast tumors only.

Original languageEnglish
Article numberR37
JournalBreast Cancer Research
Volume10
Issue number2
DOIs
Publication statusPublished - Apr 29 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tordai, A., Wang, J., Andre, F., Liedtke, C., Yan, K., Sotiriou, C., Hortobagyi, G. N., Symmans, W. F., & Pusztai, L. (2008). Evaluation of biological pathways involved in chemotherapy response in breast cancer. Breast Cancer Research, 10(2), [R37]. https://doi.org/10.1186/bcr2088