| Autor: |
Carey K Anders, Chaitanya R Acharya, David S Hsu, Gloria Broadwater, Katherine Garman, John A Foekens, Yi Zhang, Yixin Wang, Kelly Marcom, Jeffrey R Marks, Sayan Mukherjee, Joseph R Nevins, Kimberly L Blackwell, Anil Potti |
| Jazyk: |
angličtina |
| Rok vydání: |
2008 |
| Předmět: |
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| Zdroj: |
PLoS ONE, Vol 3, Iss 1, p e1373 (2008) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0001373 |
| Popis: |
To define the biology driving the aggressive nature of breast cancer arising in young women.Among 784 patients with early stage breast cancer, using prospectively-defined, age-specific cohorts (young or=65 years), 411 eligible patients (n = 200or=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.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.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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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