Age-specific differences in oncogenic pathway deregulation seen in human breast tumors. Export

@article{citeulike:3088474, abstract = {PURPOSE: To define the biology driving the aggressive nature of breast cancer arising in young women. EXPERIMENTAL DESIGN: Among 784 patients with early stage breast cancer, using prospectively-defined, age-specific cohorts (young <or=45 years; older >or=65 years), 411 eligible patients (n = 200<or=45 years; n = 211>or=65 years) with clinically-annotated Affymetrix microarray data were identified. GSEA, signatures of oncogenic pathway deregulation and predictors of chemotherapy sensitivity were evaluated within the two age-defined cohorts. RESULTS: In comparing deregulation of oncogenic pathways between age groups, a higher probability of PI3K (p = 0.006) and Myc (p = 0.03) pathway deregulation was observed in breast tumors arising in younger women. When evaluating unique patterns of pathway deregulation, a low probability of Src and E2F deregulation in tumors of younger women, concurrent with a higher probability of PI3K, Myc, and beta-catenin, conferred a worse prognosis (HR = 4.15). In contrast, a higher probability of Src and E2F pathway activation in tumors of older women, with concurrent low probability of PI3K, Myc and beta-catenin deregulation, was associated with poorer outcome (HR = 2.7). In multivariate analyses, genomic clusters of pathway deregulation illustrate prognostic value. CONCLUSION: Results demonstrate that breast cancer arising in young women represents a distinct biologic entity characterized by unique patterns of deregulated signaling pathways that are prognostic, independent of currently available clinico-pathologic variables. These results should enable refinement of targeted treatment strategies in this clinically challenging situation.}, address = {Division of Medical Oncology, Department of Medicine, Duke University, Durham, North Carolina, USA.}, author = {Anders, C. K. and Acharya, C. R. and Hsu, D. S. and Broadwater, G. and Garman, K. and Foekens, J. A. and Zhang, Y. and Wang, Y. and Marcom, K. and Marks, J. R. and Mukherjee, S. and Nevins, J. R. and Blackwell, K. L. and Potti, A.}, citeulike-article-id = {3088474}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pone.0001373}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18167534}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18167534}, doi = {10.1371/journal.pone.0001373}, issn = {1932-6203}, journal = {PLoS ONE}, keywords = {aging, bio-cancer, genome-variation, genotype-to-phenotype, molecular-signaling, regulatory-cascades}, number = {1}, posted-at = {2008-12-29 07:22:52}, priority = {2}, title = {Age-specific differences in oncogenic pathway deregulation seen in human breast tumors.}, url = {http://dx.doi.org/10.1371/journal.pone.0001373}, volume = {3}, year = {2008} }

TY - JOUR ID - citeulike:3088474 L3 - citeulike-article-id:3088474 N2 - PURPOSE: To define the biology driving the aggressive nature of breast cancer arising in young women. EXPERIMENTAL DESIGN: Among 784 patients with early stage breast cancer, using prospectively-defined, age-specific cohorts (young <or=45 years; older >or=65 years), 411 eligible patients (n = 200<or=45 years; n = 211>or=65 years) with clinically-annotated Affymetrix microarray data were identified. GSEA, signatures of oncogenic pathway deregulation and predictors of chemotherapy sensitivity were evaluated within the two age-defined cohorts. RESULTS: In comparing deregulation of oncogenic pathways between age groups, a higher probability of PI3K (p = 0.006) and Myc (p = 0.03) pathway deregulation was observed in breast tumors arising in younger women. When evaluating unique patterns of pathway deregulation, a low probability of Src and E2F deregulation in tumors of younger women, concurrent with a higher probability of PI3K, Myc, and beta-catenin, conferred a worse prognosis (HR = 4.15). In contrast, a higher probability of Src and E2F pathway activation in tumors of older women, with concurrent low probability of PI3K, Myc and beta-catenin deregulation, was associated with poorer outcome (HR = 2.7). In multivariate analyses, genomic clusters of pathway deregulation illustrate prognostic value. CONCLUSION: Results demonstrate that breast cancer arising in young women represents a distinct biologic entity characterized by unique patterns of deregulated signaling pathways that are prognostic, independent of currently available clinico-pathologic variables. These results should enable refinement of targeted treatment strategies in this clinically challenging situation. IS - 1 JF - PLoS ONE SN - 1932-6203 AD - Division of Medical Oncology, Department of Medicine, Duke University, Durham, North Carolina, USA. TI - Age-specific differences in oncogenic pathway deregulation seen in human breast tumors. VL - 3 KW - aging KW - bio-cancer KW - genome-variation KW - genotype-to-phenotype KW - molecular-signaling KW - regulatory-cascades AU - Anders, CK AU - Acharya, CR AU - Hsu, DS AU - Broadwater, G AU - Garman, K AU - Foekens, JA AU - Zhang, Y AU - Wang, Y AU - Marcom, K AU - Marks, JR AU - Mukherjee, S AU - Nevins, JR AU - Blackwell, KL AU - Potti, A PY - 2008/// UR - http://dx.doi.org/10.1371/journal.pone.0001373 ER -