%0 Journal Article
%T Age-Specific Differences in Oncogenic Pathway Deregulation Seen in Human Breast Tumors
%A Carey K. Anders
%A Chaitanya R. Acharya
%A David S. Hsu
%A Gloria Broadwater
%A Katherine Garman
%A John A. Foekens
%A Yi Zhang
%A Yixin Wang
%A Kelly Marcom
%A Jeffrey R. Marks
%A Sayan Mukherjee
%A Joseph R. Nevins
%A Kimberly L. Blackwell
%A Anil Potti
%J PLOS ONE
%D 2008
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0001373
%X 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 ¡Ü45 years; older ¡Ý65 years), 411 eligible patients (n = 200¡Ü45 years; n = 211¡Ý65 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 ¦Â-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 ¦Â-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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001373