Age-specific differences in oncogenic pathway deregulation seen in human breast tumors.
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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.
Published Version (Please cite this version)10.1371/journal.pone.0001373
Publication InfoAnders, 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.
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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
Professor 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
Professor of 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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