PROJECT ABSTRACT Fatigue, the most distressing symptom, affects between 60-90% of all individuals with breast cancer. The prevalence of fatigue increases to 80-96% when these individuals are receiving chemotherapy, a common treatment modality. This high prevalence of fatigue is a concern for clinicians, patients, and their families as fatigue is a debilitating symptom that interferes with the individual’s physical wellbeing, including their ability to perform daily activities, and decreases social functioning. However, a lack of understanding of what causes fatigue makes tailoring interventions to reduce fatigue difficult. Yet, while investigators have researched many biological pathways in relation to fatigue, one mechanism that deserves further investigation is the oral microbiome. Compelling evidence suggests that the microbiome influences symptoms such as fatigue and physical well-being. Importantly, individuals with breast cancer have been found to have dissimilar oral microbiomes to health controls, which are then further altered during chemotherapy. Additionally, studies on individuals with chronic fatigue syndrome have suggested that the oral microbiome might play a role in the development of fatigue. Given the high prevalence of fatigue experienced by individuals with breast cancer, exploring this relationship between oral microbial changes, fatigue, and physical well-being is urgently needed. Investigating the oral microbiome of individuals with breast cancer has the potential to inform our understanding of the biological process of fatigue in a cancer that affects millions of individuals annually. The objective of this longitudinal study is to inform our understanding of a biological mechanism associated with fatigue and physical well-being and clarify the impact of chemotherapy on the oral microbiome in individuals with breast cancer receiving chemotherapy. This study will use data and biospecimens that have been collected through the Duke University 1000 Patient Project (1KP). The 1KP project is an ongoing clinical data repository in which patients, including individuals with breast cancer undergoing a mastectomy, are consented for comprehensive data (demographics, disease, fatigue, and physical well-being) and biospecimen collection, such as oral microbiome samples, at multiple timepoints pre and post operatively over the course of 6 months. The aims are to: Aim 1. Characterize oral microbial changes (relative abundance, alpha diversity) prior to chemotherapy and up to 6 subsequent months in 25 individuals with breast cancer. Aim 2. Explore whether oral microbial changes (relative abundance, alpha diversity) are associated with fatigue and physical well-being measured by the Patient-Reported Outcomes Measurement Information System in 25 individuals with breast cancer receiving chemotherapy. Results from the proposed study will enhance the understanding of the relationship between the oral microbiome and fatigue in individuals with breast cancer receiving chemotherapy and inform future research on the creation of tailored intervention to ameliorate fatigue and enhance physical well-being in individuals with breast cancer.

PROJECT NARRATIVE Fatigue is the most distressing symptom for individuals with breast cancer, but the physiological pathways associated with fatigue are unclear. This study will inform whether the oral microbiome, a biologic pathway posited to impact fatigue, is associated with fatigue in individuals with breast cancer receiving chemotherapy. The study findings will provide important information that can inform mechanistic underpinnings of fatigue and guide the development of tailored interventions to manage fatigue for individuals with breast cancer.