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Evaluation of biological pathways involved in chemotherapy response in breast cancer

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 expressi...

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Detalles Bibliográficos
Autores principales: Tordai, Attila, Wang, Jing, Andre, Fabrice, Liedtke, Cornelia, Yan, Kai, Sotiriou, Christos, Hortobagyi, Gabriel N, Symmans, W Fraser, Pusztai, Lajos
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2397539/
https://www.ncbi.nlm.nih.gov/pubmed/18445275
http://dx.doi.org/10.1186/bcr2088
Descripción
Sumario: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.