Division of Hematology-Oncology
David Geffen School of Medicine
University of California
Los Angeles, California
Co-Investigator: Julienne E. Bower, PhD, David Geffen School of Medicine, University of California, Los Angeles, CA
The role of stress in breast cancer initiation and progression has long been of interest to researchers, clinicians, and patients, although empirical research on this topic has yielded mixed and inconclusive results. A major barrier to investigating linkages between stress and breast cancer has been the lack of knowledge about biological pathways that may mediate these effects.
Drs. Bower and Cole, with previous BCRF support, have completed their examination of markers of inflammation and metastasis in breast tumors from approximately 100 women originally diagnosed with early stage breast cancer. They have also conducted analyses to determine whether particular psychological characteristics were associated with different patterns of gene expression in the breast tumors and found evidence that tumors from more socially isolated women have a more pro-metastatic transcriptome profile. This discovery may be the first evidence that social stress is associated with alterations in tumor biology among women with breast cancer.
In 2013-2014, Drs. Bower and Cole will broaden their original research and extend it in a larger sample of women who have recently been diagnosed with early stage breast cancer. These women complete detailed psychosocial assessments and provide tumor and blood samples for analysis of cellular and molecular markers of inflammation before starting adjuvant therapy. Drs. Bower and Cole will continue this study for another year and recruit another 100 participants who will provide tumor specimens and blood samples for immune analysis and complete the enhanced psychosocial evaluation. This will provide an adequate sample size to examine links between psychosocial risk factors, particularly stress and social isolation, circulating monocyte populations, and tumor-associated inflammation.
Drs. Bower and Cole report significant progress in addressing the overarching aim of their project, which is to examine links between psychological stress and inflammation in breast cancer patients and underlying mechanisms. They completed data collection for a study of neural activity in women with breast cancer and healthy controls, focusing on neural responses to threat and reward. Study participants also provided blood samples for immune analysis, which are underway. Data from this study will shed light on neural mechanisms linking psychosocial stress, particularly social isolation, and aspects of the immune system known to be associated with breast cancer progression. In addition, the researchers have continued data collection for a larger study of stress and circulating and tumor-associated markers of inflammation in newly-diagnosed breast cancer patients. Specifically, they have enrolled 44 new patients into this study, for a total sample of 76 women who have completed their intensive psychosocial and immune evaluation. Finally, they are continuing to analyze tumor characteristics of socially isolated women, including gene expression analyses of tumor associated macrophages.
Dr. Steve Cole is one of the world's foremost experts on the molecular pathways by which social and environmental factors influence the activity of human, viral, and tumor genomes. He pioneered the introduction of functional genomics approaches into social and behavioral research, and has provided strategic consulting on that topic to the Institute of Medicine, the National Cancer Institute, the National Institute of Aging, the Santa Fe Institute, and the MacArthur Foundation, among others. He directs the UCLA Social Genomics Core Laboratory and the Molecular Biology Division of the UCLA Norman Cousins Center Inflammatory Biology Core.
Dr. Cole's research uses computational modeling to integrate data from epidemiologic studies, clinical natural history studies, laboratory models, and molecular and biochemical analyses to identify the physiologic signaling pathways that allow social and environmental conditions to influence the molecular pathogenesis of inflammation, infectious diseases, and cancer. Dr. Cole has mapped the molecular pathways by which social factors enhance replication of HIV-1 and HHV-8 viruses, alter expression key immune response genes such as IL-6 and Interferon-beta, and up-regulate expression of pro-metastatic genes by human breast and ovarian cancer cells. His research on social isolation’s effects on leukocyte gene expression was recognized as a Top 100 Science Story in 2007. Dr. Cole’s laboratory also discovered stress-induced plasticity of sympathetic nervous system innervation of the immune system. He has developed a diverse array of computational bioinformatics tools, including Transcript Origin Analysis to identify the cellular sources of differential gene expression and the TELiS transcription factor search engine that will be used to assess the activity of pro- and anti-inflammatory pathways in these studies. Dr. Cole also pioneered the application of that approach to assessing glucocorticoid resistance in vivo. Dr. Cole has extensive experience in DNA microarray analyses of peripheral blood leukocytes, and associated bioinformatics analyses for theory-based testing of genomic hypotheses. He will oversee the analysis and interpretation of DNA microarray data in a BCRF-supported study with Dr. Julienne Bower.