Browsing by Author "Marcom, Kelly"
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Item Open Access Age-specific differences in oncogenic pathway deregulation seen in human breast tumors.(PLoS One, 2008-01-02) Anders, Carey K; Acharya, Chaitanya R; Hsu, David S; Broadwater, Gloria; Garman, Katherine; Foekens, John A; Zhang, Yi; Wang, Yixin; Marcom, Kelly; Marks, Jeffrey R; Mukherjee, Sayan; Nevins, Joseph R; Blackwell, Kimberly L; Potti, AnilPURPOSE: 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=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. 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.Item Open Access The Project Baseline Health Study: a step towards a broader mission to map human health.(NPJ digital medicine, 2020-01) Arges, Kristine; Assimes, Themistocles; Bajaj, Vikram; Balu, Suresh; Bashir, Mustafa R; Beskow, Laura; Blanco, Rosalia; Califf, Robert; Campbell, Paul; Carin, Larry; Christian, Victoria; Cousins, Scott; Das, Millie; Dockery, Marie; Douglas, Pamela S; Dunham, Ashley; Eckstrand, Julie; Fleischmann, Dominik; Ford, Emily; Fraulo, Elizabeth; French, John; Gambhir, Sanjiv S; Ginsburg, Geoffrey S; Green, Robert C; Haddad, Francois; Hernandez, Adrian; Hernandez, John; Huang, Erich S; Jaffe, Glenn; King, Daniel; Koweek, Lynne H; Langlotz, Curtis; Liao, Yaping J; Mahaffey, Kenneth W; Marcom, Kelly; Marks, William J; Maron, David; McCabe, Reid; McCall, Shannon; McCue, Rebecca; Mega, Jessica; Miller, David; Muhlbaier, Lawrence H; Munshi, Rajan; Newby, L Kristin; Pak-Harvey, Ezra; Patrick-Lake, Bray; Pencina, Michael; Peterson, Eric D; Rodriguez, Fatima; Shore, Scarlet; Shah, Svati; Shipes, Steven; Sledge, George; Spielman, Susie; Spitler, Ryan; Schaack, Terry; Swamy, Geeta; Willemink, Martin J; Wong, Charlene AThe Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum. Enrolled participants will be evaluated serially using clinical, molecular, imaging, sensor, self-reported, behavioral, psychological, environmental, and other health-related measurements. An initial deeply phenotyped cohort will inform the development of a large, expanded virtual cohort. The PBHS will contribute to precision health and medicine by integrating state of the art testing, longitudinal monitoring and participant engagement, and by contributing to the development of an improved platform for data sharing and analysis.