Understanding factors that influence breast cancer risk, disease progression and treatment outcomes
: (Alternative Format Thesis)

  • Ainhoa Arana Echarri

Student thesis: Doctoral ThesisPhD


Breast cancer is the most common form of cancer among women worldwide. Although survival has increased due to advances in diagnosis and treatment, heterogeneity in the clinical response remains a challenge. Understanding factors influencing cancer outcomes, and examining whether these factors can be modified, will benefit clinical management and post-treatment care. Given that the number of women living with and beyond breast cancer is increasing, there is a need for research examining whether interventions, such as exercise and physical activity, influence factors mechanistically implicated in disease progression, which might explain relationships between an active lifestyle and breast cancer recurrence or survival. Evidence shows that chronic inflammation and immune dysfunction influence tumorigenesis and tumour progression. Indeed, these immunological processes are influenced by, age, exercise, physical activity level, cardiorespiratory fitness and body composition: characteristics which are also linked to cancer outcomes. The mechanisms underlying these interactions remain to be fully elucidated. For the first time, the present thesis examined mechanistic processes implicated in cancer risk and disease progression, including immune impairment and adipose tissue dysfunction, while in parallel, measuring participant characteristics, known to influence cancer outcomes, including age, body composition and cardiorespiratory fitness. Furthermore, this thesis also investigated the ability of exercise interventions to influence and/or modify these processes. Chapter 2 reviewed relevant literature providing evidence over the influence of inter-individual participant characteristics on clinical outcomes and current or emerging biomarkers of treatment response. Chapter 2 highlighted the need for an integrative phenomic approach in research and clinical practice, which interprets clinical biomarkers with objective measurements of broader patient characteristics. Chapter 3 demonstrated differences in blood immune cell profiles of breast cancer survivors compared to healthy women. These differences, which likely reflect immunosenescence, perhaps caused by cancer or its treatment, were influenced by participant characteristics, such as cardiorespiratory fitness and adiposity, in a cell type-dependent manner. Chapters 4 and 5 demonstrated that regular exercise training among breast cancer survivors influences immune cell profiles, basal unstimulated activation of T cells, and T cell recognition of virus and tumour antigens, which could be interpreted as anti-immunosenescence and pro-immunosurveillance effects of exercise. Finally, Chapter 6 demonstrated anti-inflammatory and anti-immunosenescence effects of regular exercise training – among overweight and obese people considered to be at higher risk of cancer – likely mediated, at least partly, by changes within adipose tissue. In summary, the investigations in this thesis have expanded our understanding of mechanistic processes implicated in cancer risk, disease progression, and survival and have provided a novel contribution by examining the influence of factors associated with a physically active lifestyle.
Date of Award29 Mar 2023
Original languageEnglish
Awarding Institution
  • University of Bath
SponsorsGW4 Biomed MRC DTP
SupervisorJohn Campbell (Supervisor), James Turner (Supervisor), Dylan Thompson (Supervisor), Mark Beresford (Supervisor), Rachel Butler (Supervisor) & Robert H. Jones (Supervisor)

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