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

dc.contributor.author Anders, Carey K
dc.contributor.author Acharya, Chaitanya R
dc.contributor.author Hsu, David S
dc.contributor.author Broadwater, Gloria
dc.contributor.author Garman, Katherine
dc.contributor.author Foekens, John A
dc.contributor.author Zhang, Yi
dc.contributor.author Wang, Yixin
dc.contributor.author Marcom, Kelly
dc.contributor.author Marks, Jeffrey R
dc.contributor.author Mukherjee, Sayan
dc.contributor.author Nevins, Joseph R
dc.contributor.author Blackwell, Kimberly L
dc.contributor.author Potti, Anil
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:31:22Z
dc.date.issued 2008-01-02
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/18167534
dc.identifier.uri https://hdl.handle.net/10161/4481
dc.description.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.
dc.language eng
dc.language.iso en_US
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0001373
dc.subject Adult
dc.subject Age Factors
dc.subject Aged
dc.subject Breast Neoplasms
dc.subject Cohort Studies
dc.subject Female
dc.subject Humans
dc.subject Middle Aged
dc.subject Oncogenes
dc.title Age-specific differences in oncogenic pathway deregulation seen in human breast tumors.
dc.title.alternative
dc.type Journal article
duke.contributor.id Marcom, Kelly|0115774
duke.contributor.id Marks, Jeffrey R|0098991
duke.contributor.id Nevins, Joseph R|0084291
duke.contributor.id Blackwell, Kimberly L|0047570
dc.description.version Version of Record
duke.date.pubdate 2008-1-2
duke.description.issue 1
duke.description.volume 3
dc.relation.journal Plos One
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/18167534
pubs.begin-page e1373
pubs.issue 1
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Faculty
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Gastroenterology
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group Pathology
pubs.organisational-group Radiation Oncology
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Surgical Sciences
pubs.publication-status Published online
pubs.volume 3
dc.identifier.eissn 1932-6203
duke.contributor.orcid Marcom, Kelly|0000-0001-5302-6368


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