Author ORCID Identifier

https://orcid.org/0000-0003-3513-655X

Semester

Summer

Date of Graduation

2025

Document Type

Dissertation (Campus Access)

Degree Type

PhD

College

School of Medicine

Department

Exercise Physiology

Committee Chair

Emidio Pistilli

Committee Member

Randy Bryner

Committee Member

Ida Holaskova

Committee Member

John Hollander

Committee Member

Beth Vettiyil

Abstract

Early-stage breast cancer (BC) is the most commonly diagnosed malignancy among women, and despite successful advancements in early diagnosis and treatment, cancer related fatigue remains a substantial challenge that persists long into survivorship. This dissertation focuses on the clinical measurement of body composition dynamics in early-stage BC, with emphasis on alterations that may reflect underlying pathophysiological mechanisms that manifest as symptomatic fatigue and functional decline. Traditional techniques used in the clinic to assess body composition and function have been unsuccessful in translating the applications proposed by existing pre-clinical findings. Using computed tomography (CT) imaging, we reveal previously unidentified changes in body composition and tissue morphology throughout neoadjuvant chemotherapy in patients with non- metastatic BC. Despite stability in body weight exhibited by most patients, non-metastatic BC was characterized by consistent declines to muscle quality alongside indicators of remodeling in subcutaneous adipose tissue. Mechanistically, these findings reflect the clinical implications of inflammation, hormonal dysregulation, and mitochondrial dysfunction that drive persistent fatigue and functional impairments experienced by patients and survivors of early-stage BC. This work highlights the value afforded by advanced imaging techniques that are able to capture subtle, though clinically relevant, changes that shape the patient experience. Understanding these underlying morphologic changes in skeletal muscle and adipose tissue depots is fundamental for personalizing patient care aimed at preserving functional independence that is underscored by existing risk stratification criteria regarding cachexia.

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