Julienne E. Bower - US grants

DESCRIPTION (provided by applicant): The broad goal of this research proposal is to elucidate the basic mechanisms underlying radiation-induced fatigue in patients with localized breast or prostate cancer, focusing on psychological and immunological factors that may contribute to fatigue during and after treatment. Preliminary studies conducted by our group have identified psychological and immune parameters associated with fatigue in breast cancer survivors, including several markers of immune activation. Pilot testing will first be conducted to determine which of these immune parameters are influenced by radiation treatment. The main phase of the study will involve a prospective, longitudinal examination of 150 breast and prostate cancer patients receiving external beam radiation therapy. Subjects will be recruited from the UCLA Radiation Oncology Clinic and will be assessed psychologically and immunologically before treatment onset, at biweekly time points during treatment, and at three longer-term follow-ups. The specific aims of the study are: 1) to determine whether changes in the immune system induced by radiation therapy are associated with changes in fatigue, 2) to evaluate the role of psychosocial factors as predictors and correlates of radiation-induced fatigue, 3) to evaluate the effects of irradiated site and treatment volume on fatigue, and 4) to identify individuals whose fatigue does not remit following treatment and determine the correlates of acute vs. more enduring fatigue. Information gained from this project will advance our understanding of radiation-induced fatigue, thereby paving the way for the development of interventions to help manage and reduce this problem and improve quality of life for cancer patients receiving radiation therapy. The proposed research project will enhance the candidate's existing research skills in health psychology and psychoneuroimmunology and promote the development of new skills necessary for an academic career in cancer prevention and control. Together with a targeted program of didactic instruction, this project will prepare the candidate to become a fully independent behavioral scientist in the field of cancer prevention and control research.

psychological adaptation; breast neoplasms; breast neoplasm /cancer diagnosis; psychological aspect of cancer; women's health; psychological stressor; motivation; immunology; endocrinology; self concept; emotions; behavioral /social science research tag; human subject; female; clinical research;

[unreadable] DESCRIPTION (provided by applicant): There are currently over 2 million breast cancer survivors in the United States, many of whom experience persistent cancer-related symptoms. Fatigue is the most common and distressing symptom among women successfully treated for breast cancer and causes serious disruption in quality of life. Mind-body interventions such as yoga are popular among cancer patients and have shown beneficial effects on fatigue in other populations; however, yoga trials in cancer are scarce. Based on promising results from a small, single-arm pilot study, the proposed study will evaluate the feasibility, acceptability, and preliminary efficacy of an lyengar yoga intervention for breast cancer survivors with persistent fatigue. In this randomized, controlled trial, 60 breast cancer survivors with persistent cancer-related fatigue will be randomly assigned to yoga or health education control for 12 weeks and followed for 3 months. The aims of the project are to: 1) determine the feasibility and acceptability of a 12-week lyengar yoga intervention for breast cancer survivors with persistent fatigue as compared with health education control; 2) evaluate the effects of yoga vs. health education on fatigue and physical performance in breast cancer survivors with persistent fatigue; and 3) explore the effects of yoga vs. health education on behavioral and immune outcomes associated with cancer- related fatigue, including depressed mood, sleep, pain, proinflammatory cytokine activity, and quality of life. This project will constitute the first randomized, controlled trial of yoga for fatigue in breast cancer survivors and will provide key preliminary data to support a larger efficacy trial. In addition, the study will provide insight into secondary effects of yoga and generate hypotheses about potential mechanisms for intervention effects that can be systematically evaluated in a larger trial. The development of targeted treatments for cancer-related fatigue is critical for maintaining quality of life in the growing population of breast cancer survivors. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Fatigue is one of the most common and distressing side effects of breast cancer treatment and may persist for months or years after successful treatment completion. Approximately one-third of breast cancer survivors report moderate to severe symptoms of fatigue, which has a negative impact on all aspects of quality of life. Although the prevalence and impact of cancer-related fatigue has now been well established, very little is known about predictors and mechanisms for the development and persistence of fatigue post-treatment. Accordingly, the primary goal of this prospective, longitudinal study is to identify biological and psychological risk factors for post-treatment fatigue, with intensive evaluation of mechanisms, in women newly diagnosed with early stage breast cancer. In particular, this application focuses on vulnerability factors that increase risk for inflammatory processes given evidence suggesting an inflammatory basis for cancer-related fatigue. Specific aims are to: 1) determine whether inflammatory risk genes, hypothalamic-pituitary-adrenal axis dysregulation, and body mass index at treatment onset predict post-treatment fatigue in breast cancer patients assessed longitudinally for 18 months after treatment completion; 2) evaluate whether history of depression and early life stress at treatment onset predict post-treatment fatigue in breast cancer patients assessed longitudinally for 18 months after treatment onset; 3) investigate the contribution of measured proinflammatory cytokine activity to the association between biological and psychological risk factors and post-treatment fatigue. We will recruit 360 women with newly-diagnosed, early-stage breast cancer before initiation of treatment with radiation, chemotherapy, trastuzumab or endocrine therapy. At baseline, participants will complete self-report questionnaires, diagnostic interview for depression, blood draw for cytokine gene polymorphisms and markers of inflammation, and saliva samples for diurnal cortisol slope. Follow-up assessments conducted at treatment completion and at 6, 12, and 18 months post-treatment will determine the trajectory of post-treatment fatigue and associated changes in inflammatory processes. This research is a critical next step in the early identification of patients who are at risk for persistent fatigue as a long term side effect of cancer treatment and for the development and implementation of targeted interventions to prevent and treat this disabling symptom.

DESCRIPTION (provided by applicant): The proposed new UCLA program will train predoctoral students from the behavioral and social sciences in biomedical theory, evidence, and methods and mentor them to integrate these approaches into health research. The goal is to train interdisciplinary investigators based in population science and health psychology who examine the complex pathways through which demographic, socioeconomic, and psychological processes influence and are influenced by health and disease. The program is a partnership of the UCLA California Center for Population Research (CCPR) and the Program in Health Psychology in the Department of Psychology. The CCPR and the Program in Health Psychology are top centers nationally for research in their respective areas. We request support for 5 predoctoral trainees per year for two year traineeships. Trainees will be selected from students in psychology, sociology, community health sciences, and economics. In the first year, trainees will take a carefully designed year-long didactic training course taught by life sciences and biomedical faculty focusing on the structure and function of key bodily systems which are critical for health and disease and the pathophysiology of major medical conditions. They will also develop a research proposal with two co-mentors, one from the behavioral or population sciences, and one from the biomedical sciences. In the second year, students will apply their first-year coursework via a sequence of laboratory and research experiences. By the end of their second year, trainees will complete an independent research project based on their proposal, co-mentored by a biomedical science faculty member and a population or behavioral science faculty member, and yielding either a dissertation proposal or a manuscript to be submitted for publication. Throughout the traineeship they will participate in a proseminar with faculty and guest speakers that integrate the biomedical knowledge into their scientific approaches. The program will be led by a team of faculty from the population, behavioral, and biomedical sciences that will be overseen and supported by a similarly interdisciplinary committee of Core Faculty. To mentor trainees, provide laboratory and research experiences, and lecture in the didactic training course, we have recruited a large team of distinguished faculty from the population, behavioral, biomedical sciences with outstanding records of publication, extramural funding, and mentoring, as well as extensive experience in collaboration on health research across traditional disciplinary boundaries. Relevance: The program will benefit public health by producing new interdisciplinary investigators who through their research will help to determine the pathways by which individual social, economic, and psychological factors influence and are influenced by health and disease. By virtue of this training, this new cohort of investigators will be better able to identify interdisciplinary approaches to intervention for the benefit of public health in the United States.

PROJECT SUMMARY Breast cancer is the most common cancer in women younger than 50 years, accounting for up to 25% of new breast cancer cases. Improved survival after a breast cancer diagnosis has focused attention on the critical need to address the impact of the disease and its treatments on long-term outcomes in younger women. This has become an increasingly important cancer control priority, including federal legislation focusing on the unique needs of women <45 years old. Studies have consistently shown that younger women have greater psychological and physical morbidity after breast cancer than older women and age-matched women with no cancer history, including elevated levels of depression and other behavioral symptoms (i.e., fatigue, sleep disturbance, vasomotor symptoms) that cause significant impairment in quality of life. Increased behavioral symptoms have been documented up to 10 years after diagnosis in this population, suggesting that effects may not remediate without intervention. Younger breast cancer survivors are at risk for adverse long-term effects, making them a particularly vulnerable population, for whom only a few specific interventions have been tested. A major barrier to adoption of many behavioral interventions is the lack of a translational research implementation strategy, and thus these interventions fail to become a standard of care that is clinically provided and reimbursed. To meet this challenge, we will conduct a phase III, three-group, randomized clinical trial at three geographically separated NCI-designated comprehensive cancer centers, randomly assigning 360 younger post-treatment breast cancer survivors, to one of two promising interventions (survivorship education or mindful awareness practices), comparing each to a usual care/waitlist control group. We hypothesize that both of the intervention programs will be effective in reducing behavioral symptoms (depression - primary outcome; fatigue, sleep disturbance, vasomotor symptoms-secondary outcomes) over a 6 month post- intervention period, in comparison to the usual care/waitlist control group. Additionally, we will examine the efficacy of the interventions relative to the control group on circulating and genomic markers of inflammation, hypothesizing that the mindfulness intervention will significantly reduce markers of inflammation. Finally, we will explore potential moderators of intervention efficacy in the intervention groups.

Project summary Breast cancer is the most common cancer in women, with over two-hundred and sixty thousand new cases expected in the United States in 2018 alone. There are estimated to be more than 3 million breast cancer survivors in the US due to substantial advances in detection and treatment, with this number continuing to grow. However, treatments also increase risk for long-term and late toxicities, including effects on physical and cognitive function that interfere with quality of life. One possible explanation recently proposed is that the toxicity of cancer treatments may directly accelerate the aging process in some patients, leading to earlier onset of age-related symptoms such as cognitive complaints, fatigue, declines in physical function, and lasting pain. However, this hypothesis has not been rigorously tested in clinical populations. Our study will examine the effects of common breast cancer treatments as they relate to markers of biological aging, inflammation, and reports of physical and cognitive complaints in a prospective study of breast cancer patients assessed prior to and after exposure to chemotherapy and/or radiotherapy. The proposed study will leverage an existing NCI- funded cohort of women with early-stage breast cancer assessed before onset of adjuvant therapy with radiation (RT), chemotherapy (CT), or endocrine therapy and again after completion of RT and/or CT and at follow-up visits occurring 6-, 12-, and 18-month post-treatment, with serial blood specimens for plasma, DNA and RNA analyses. In this well characterized cohort of breast cancer survivors, we propose to add the assessment of markers of biological aging using existing collected specimens and add a new behavioral assessment at 7 years post treatment to 1) examine the effects of breast cancer treatments on the biological aging process, 2) test the relationship between accelerated biological aging and cognitive and physical complaints in breast cancer patients over the follow-up period, and 3) test whether inflammatory factors mediate the relationship between biological aging and cognitive and physical complaints.