Although advancements in breast cancer treatments have resulted in improved rates of survival, a majority of women with breast cancer (BC) experience distressing symptoms during treatment, which for some, persist into survivorship. The symptoms most frequently reported among women with BC include cognitive dysfunction (CD), depressive symptoms, anxiety, fatigue, sleep disturbances, and pain, which may be collectively called """"""""psychoneurological (PN) symptoms."""""""" Inflammatory activation and epigenetic alterations have been associated with the etiology of cancer and with various chronic neurocognitive disorders. However, to date, no investigators have considered these epigenetic processes as possible mechanisms associated with the etiology of PN symptoms in women with BC. Given that epigenetic patterns have been shown to have plasticity, the further elucidation of the relationship of epigenetic alterations to the development and persistence of PN symptoms could provide foundational knowledge for the future development of predictive markers and treatments to address the epigenetic changes associated with PN symptoms in women with BC. Therefore, the specific aims of this study are to examine: 1. The frequency and severity of PN symptoms and the interrelationships among PN symptoms at each time point. 2. Levels of inflammation and to quantify the frequency and genome-wide localization of changes in epigenetic patterns across time following chemotherapy. 3. The relationships among inflammation, epigenetic changes, and the development, severity, and persistence of PN symptoms across time. To meet these aims, the proposed study will prospectively characterize PN symptoms (cognitive dysfunction;depressive symptoms and anxiety;fatigue;sleep disturbances;pain), inflammatory activation [(levels of C- reactive protein (CRP), tumor necrosis factor alpha (TNF-a), interleukin 1 beta (IL-1B), and interleukin 6 (IL- 6)], and epigenetic alterations in 75 women diagnosed with early-stage BC across 5 timepoints: prior to their receipt of chemotherapy, at the time of their fourth chemotherapy treatment, and at 6, 12, and 24 months following the initiation of chemotherapy. Epigenetic alterations will be detected by quantifying the: (1) frequency and genome-wide location of methylation;(2) expression of a histone methyltransferease, EZH2, which is a Polycomb group protein that is thought to be important for the early steps in the epigenetic """"""""decision"""""""" process;and (3) telomere attrition, which can lead to alterations in chromatin compaction/gene expression. The study results may potentially deepen understanding regarding the biological processes underlying PN symptoms and lead to improved strategies for symptom management in women with BC.

Public Health Relevance

Distressing symptoms are frequently reported among women with BC over the treatment period, which may result in a significant decline in quality of life and health outcomes over the active treatment period and into survivorship. The proposed study may identify epigenetic alterations and biobehavioral mechanisms associated with distressing symptoms in women with BC that can be used to develop targeted interventions to reduce symptoms, enhance quality of life and possibly prevent or reverse the adverse health outcomes associated with BC and its treatment.

National Institute of Health (NIH)
National Institute of Nursing Research (NINR)
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Special Emphasis Panel (ZNR1-REV-T (02))
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Tully, Lois
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Virginia Commonwealth University
Other Health Professions
Schools of Nursing
United States
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Oliveira, Tadeu; Starkweather, Angela; Ramesh, Divya et al. (2018) Putative mechanisms of cognitive decline with implications for clinical research and practice. Nurs Forum :
Lyon, Debra E; Starkweather, Angela; Yao, Yingwei et al. (2018) Pilot Study of Metabolomics and Psychoneurological Symptoms in Women With Early Stage Breast Cancer. Biol Res Nurs 20:227-236
Starkweather, Angela; Kelly, Debra Lynch; Thacker, Leroy et al. (2017) Relationships among psychoneurological symptoms and levels of C-reactive protein over 2 years in women with early-stage breast cancer. Support Care Cancer 25:167-176
Wright, Michelle L; Dozmorov, Mikhail G; Wolen, Aaron R et al. (2016) Establishing an analytic pipeline for genome-wide DNA methylation. Clin Epigenetics 8:45
Starkweather, Angela R; Heineman, Amy; Storey, Shannon et al. (2016) Methods to measure peripheral and central sensitization using quantitative sensory testing: A focus on individuals with low back pain. Appl Nurs Res 29:237-41
Lyon, Debra E; Cohen, Ronald; Chen, Huaihou et al. (2016) The relationship of cognitive performance to concurrent symptoms, cancer- and cancer-treatment-related variables in women with early-stage breast cancer: a 2-year longitudinal study. J Cancer Res Clin Oncol 142:1461-74
Chakradeo, Shweta; Elmore, Lynne W; Gewirtz, David A (2016) Is Senescence Reversible? Curr Drug Targets 17:460-6
Wright, Michelle L; Starkweather, Angela R; York, Timothy P (2016) Mechanisms of the Maternal Exposome and Implications for Health Outcomes. ANS Adv Nurs Sci 39:E17-30
Lyon, Debra E; Cohen, Ronald; Chen, Huaihou et al. (2016) Relationship of systemic cytokine concentrations to cognitive function over two years in women with early stage breast cancer. J Neuroimmunol 301:74-82
Starkweather, Angela R; Lyon, Debra E; Kinser, Patricia et al. (2016) Comparison of Low Back Pain Recovery and Persistence: A Descriptive Study of Characteristics at Pain Onset. Biol Res Nurs 18:401-10

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