TY - JOUR
T1 - Evaluation of biological pathways involved in chemotherapy response in breast cancer
AU - Tordai, Attila
AU - Wang, Jing
AU - Andre, Fabrice
AU - Liedtke, Cornelia
AU - Yan, Kai
AU - Sotiriou, Christos
AU - Hortobagyi, Gabriel N.
AU - Symmans, W. Fraser
AU - Pusztai, Lajos
N1 - Funding Information:
Supported by grants to L.P. from the NCI (RO1-CA106290), the Breast Cancer Research Foundation, and the Goodwin Foundation and to G.N.H. by the Nellie B. Connally Breast Cancer Research Fund. T.A. is a visiting professor of the Hungarian American Enterprise Scholarship Fund (HAESF). F.A is supported by Fondation de France, Fondation Lilly and a career development award from the American Society of Clinical Oncology. C.L. is supported by the Deutsche Forschungsgemeinschaft.
PY - 2008/4/29
Y1 - 2008/4/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=48949119363&partnerID=8YFLogxK
U2 - 10.1186/bcr2088
DO - 10.1186/bcr2088
M3 - Article
C2 - 18445275
AN - SCOPUS:48949119363
SN - 1465-5411
VL - 10
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 2
M1 - R37
ER -