Age-specific differences in oncogenic pathway deregulation seen in human breast tumors.
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.
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https://hdl.handle.net/10161/4481Published Version (Please cite this version)
10.1371/journal.pone.0001373Publication Info
Anders, Carey K; Acharya, Chaitanya R; Hsu, David S; Broadwater, Gloria; Garman, Katherine;
Foekens, John A; ... Potti, Anil (2008). Age-specific differences in oncogenic pathway deregulation seen in human breast tumors.
PLoS One, 3(1). pp. e1373. 10.1371/journal.pone.0001373. Retrieved from https://hdl.handle.net/10161/4481.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Chaitanya Acharya
Research Associate, Senior
I utilize computational biology, machine learning and pre-clinical mouse models to
study cancer. My long-term research interests involve developing a comprehensive understanding
of immune response to changing tumor microenvironment and its role in tumor progression
and resistance to therapy.
Kimberly Lynn Blackwell
Adjunct Professor in the Department of Medicine
Breast cancer angiogenesis Breast cancer in younger women Hormonal therapy Neoadjurant
therapy for breast cancer Current Clinical Investigations Principal Investigator,
A Phase I-II Study of Neoadjuvant Evacet/Paclitaxel/Hyperthermia in Locally Advanced
Breast Cancer Patients. Investigator, Development of Screening Markers for Breast
Cancer using Circulating Immune Complexes: Collaborative Study with Diagen Medical
Technologies. P
Paul Kelly Marcom
Adjunct Professor in the Department of Medicine
Basic Science: -Germline and somatic genetic changes in breast cancer. Translational:
-Identification and management of individuals and families with hereditary cancer
risk. -Communication of cancer risk information to individuals and families. -Breast
cancer prevention. -Optimizing management of early breast cancer. -Treatment of metastatic
breast cancer Clinically, Dr. Marcom works as a medical oncologist in the multidisciplina
Jeffrey R. Marks
Joseph W. and Dorothy W. Beard Distinguished Professor of Experimental Surgery
I have been engaged in basic and applied cancer research for over 28 years beginning
with my post-doctoral fellowship under Arnold Levine at Princeton. Since being appointed
to the faculty in the Department of Surgery at Duke, my primary interest has been
towards understanding breast and ovarian cancer. I am a charter member of the NCI-Early
Detection Research Network (EDRN) and have been an integral scientist in the breast
and gynecologic collaborative group for 15 years including leading th
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