Evaluation of biological pathways involved in chemotherapy response in breast cancer Export

@article{citeulike:2740970, 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.}, author = {Tordai, Attila and Wang, Jing and Andre, Fabrice and Liedtke, Cornelia and Yan, Kai and Sotiriou, Christos and Hortobagyi, Gabriel N. and Symmans, Fraser W. and Pusztai, Lajos}, citeulike-article-id = {2740970}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/bcr2088}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18445275}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18445275}, day = {29}, doi = {10.1186/bcr2088}, issn = {1465-5411}, journal = {Breast Cancer Research}, keywords = {biological, breast, cancer, cancer-crosstalk, chemotherapy, pathways, response, subtypes}, month = {April}, pages = {R37+}, posted-at = {2008-09-09 13:23:06}, priority = {4}, title = {Evaluation of biological pathways involved in chemotherapy response in breast cancer}, url = {http://dx.doi.org/10.1186/bcr2088}, volume = {10}, year = {2008} }

TY - JOUR ID - citeulike:2740970 L3 - citeulike-article-id:2740970 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. JF - Breast Cancer Research SN - 1465-5411 TI - Evaluation of biological pathways involved in chemotherapy response in breast cancer VL - 10 SP - R37 KW - biological KW - breast KW - cancer KW - cancer-crosstalk KW - chemotherapy KW - pathways KW - response KW - subtypes AU - Tordai, Attila AU - Wang, Jing AU - Andre, Fabrice AU - Liedtke, Cornelia AU - Yan, Kai AU - Sotiriou, Christos AU - Hortobagyi, Gabriel AU - Symmans, Fraser AU - Pusztai, Lajos PY - 2008/04/29/ UR - http://dx.doi.org/10.1186/bcr2088 ER -