Julienne E. Bower, PhD

2012-2013 BCRF Project:
(made possible by generous support from Clinique)
Co-Investigator: Steven W. Cole, 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. Over the past decade, inflammation has emerged as a plausible biological pathway linking stress and breast cancer outcomes. The role of inflammation in tumor growth and progression is now well established, with tumor-associated inflammatory cells including macrophages facilitating many of the hallmark characteristics of cancer (e.g. proliferation, angiogenesis, resistance to cell death, invasion, metastasis). There is also compelling evidence linking inflammation and psychological stress. In the laboratory, chronic stress is seen to increase macrophage trafficking and activation, leading to increased production of pro-inflammatory cytokines. In clinical studies, exposure to acute (e.g. public speaking) and chronic stressors (e.g. caregiving, chronic interpersonal problems) has been reliably linked with increases in pro-inflammatory cytokine activity.

Earlier preclinical data from Drs. Bower and Cole offer initial support for the hypothesis that stress may induce breast cancer progression via effects on inflammatory processes, specifically effects on tumor-associated macrophages. Although research on stress and inflammation in clinical cancer populations is extremely limited, preliminary evidence suggests a link between psychological stress and tumor-associated markers of inflammation in women with ovarian cancer. However, the relationship between stress and inflammatory processes, particularly in the tumor microenvironment, has not been examined in breast cancer patients.

Drs. Bower and Cole are currently enrolling women with early stage breast cancer to evaluate the association between chronic psychological stress and tumor-associated immune responses. They are conducting interviews with women to assess stressful events that may have occurred throughout their lifetimes and particularly in the years prior to cancer diagnosis. In addition, they are collecting tumor samples from these women to determine whether there are links between stress exposure and immune cells in the tumor microenvironment that may predispose to negative clinical outcomes. This work aims to advance our understanding of links between psychological stress and breast cancer and identify possible targets for intervention.

Mid-year Progress: This project continues to investigate links between psychological stress and characteristics of immune cells known to be important for the growth and spread of breast tumors. Macrophages are a type of immune cell that plays a key role in tumor initiation, progression, and metastasis. Macrophages appear to be sensitive to psychological stress in healthy individuals, but these links have not been evaluated in breast cancer patients. In the current study, Drs. Bower and Cole are examining the association between lifetime stress exposure and tumor-promoting macrophages in newly diagnosed breast cancer patients and in healthy breast cancer survivors. In addition, they are investigating the neural underpinnings of chronic stress exposure to determine how stress may become embedded in the brain to influence cancer progression.

Drs. Bower and Cole are currently in the process of analyzing data to determine whether women with high lifetime stress exposure show elevated inflammatory/metastatic gene expression. As their current year's BCRF project is designed to expand upon this work to provide a more integrated understanding of the mechanisms through which stress may impact inflammation and ultimately, tumor progression/spread, they are focusing on circulating monocyte populations, which they were not able to assess the our initial study as women were never brought into the lab. The research team is now recruiting newly diagnosed breast cancer patients from their ongoing NCI-funded R01, which focuses on biobehavioral predictors of fatigue in women with early stage breast cancer. To date, they have established relationships with oncologists at UCLA and other practices in the Los Angeles area and have developed procedures for collection and processing of the interview and immune data.

Drs. Bower and Cole are also conducting a more in-depth follow-up with the breast cancer survivors from their earlier study, where participants will undergo an in-person assessment designed to identify the neurobiological mechanisms through which stress influences inflammatory biology. Investigators will collect blood samples for immune analysis, focusing on circulating monocyte populations that have been implicated in tumor progression and enable them to examine the association between lifetime stress exposure, numbers of immature pro-inflammatory monocytes (CD16-/CD14+ leukocytes), circulating markers of inflammation (IL-6, CRP), and monocyte expression of gene transcripts involved in inflammation, chemotaxis, and other biological hallmarks of the pro-inflammatory monocyte subpopulation.

In addition, Drs. Bower and Cole plan to conduct neuroimaging with a subset of these breast cancer survivors, which will enable them to examine the neural mechanisms through which stress may become "embedded" in the brain to influence downstream biological processes, including inflammation. They plan to leverage new findings in this area to elucidate links between stress and inflammation in women with breast cancer.

Bio:
Dr. Bower is Associate Professor of Psychology and Psychiatry/Biobehavioral Sciences at the University of California, Los Angeles, research scientist at the UCLA Cousins Center for Psychoneuroimmunology in the Semel Institute, and a member of the Jonsson Comprehensive Cancer Center. Dr. Bower earned her PhD in psychology from UCLA and completed postdoctoral training in psychoneuroimmunology and cancer prevention/control at UCLA with another BCRF awardee, Dr. Patricia Ganz.

Dr. Bower's research focuses broadly on biobehavioral processes in breast cancer with the goal of understanding how interactions between the brain, behavior, and the immune system influence health and well-being in cancer patients and survivors. One area of her work examines biological mechanisms underlying fatigue and other behavioral side effects of cancer treatment, including depression, cognitive problems, and sleep disturbance. Another area that Dr. Bower investigates is the impact of stress on inflammatory and metabolic processes and disease-relevant health behaviors in women with breast cancer. She is also testing mind-body interventions designed to reduce stress and fatigue, including yoga, tai chi, and mindfulness meditation, and examining intervention effects on immune and endocrine pathways. Dr. Bower has received awards from the Psychoneuroimmunology Research Society and the American Psychological Association (Health Psychology) in recognition of her work.