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.

Public Health Relevance

With advances in detection and treatment, the number of women who survive breast cancer has increased significantly in recent years. Many of these women will experience persistent, debilitating fatigue after completing cancer treatment. This research will identify risk factors for post-treatment fatigue and illuminate the biological underpinnings of this symptom, facilitating the early identification of vulnerable patients and the development and implementation of targeted therapies.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Alfano, Catherine M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Overall Medical
Los Angeles
United States
Zip Code
Boyle, Chloe C; Kuhlman, Kate R; Dooley, Larissa N et al. (2018) Inflammation and dimensions of reward processing following exposure to the influenza vaccine. Psychoneuroendocrinology 102:16-23
Kuhlman, Kate Ryan; Boyle, Chloe C; Irwin, Michael R et al. (2017) Childhood maltreatment, psychological resources, and depressive symptoms in women with breast cancer. Child Abuse Negl 72:360-369
Kuhlman, Kate Ryan; Irwin, Michael R; Ganz, Patricia A et al. (2017) Cortisol Awakening Response as a Prospective Risk Factor for Depressive Symptoms in Women After Treatment for Breast Cancer. Psychosom Med 79:763-769
Bower, Julienne E; Irwin, Michael R (2016) Mind-body therapies and control of inflammatory biology: A descriptive review. Brain Behav Immun 51:1-11
Dooley, Larissa N; Ganz, Patricia A; Cole, Steve W et al. (2016) Val66Met BDNF polymorphism as a vulnerability factor for inflammation-associated depressive symptoms in women with breast cancer. J Affect Disord 197:43-50
Crosswell, Alexandra D; Lockwood, Kimberly G; Ganz, Patricia A et al. (2014) Low heart rate variability and cancer-related fatigue in breast cancer survivors. Psychoneuroendocrinology 45:58-66
Bower, Julienne E; Crosswell, Alexandra D; Slavich, George M (2014) Childhood Adversity and Cumulative Life Stress: Risk Factors for Cancer-Related Fatigue. Clin Psychol Sci 2:
Bower, Julienne E (2014) Cancer-related fatigue--mechanisms, risk factors, and treatments. Nat Rev Clin Oncol 11:597-609
Bower, Julienne E; Lamkin, Donald M (2013) Inflammation and cancer-related fatigue: mechanisms, contributing factors, and treatment implications. Brain Behav Immun 30 Suppl:S48-57