Author Identifier
Date of Award
2026
Keywords
Chemotherapy, immune system, fasting, caloric restriction, exercise
Document Type
Thesis
Publisher
Edith Cowan University
Degree Name
Doctor of Philosophy
School
School of Medical and Health Sciences
First Supervisor
Robert Newton
Second Supervisor
Daniel Galvao
Third Supervisor
Dennis Taaffe
Fourth Supervisor
Carolyn McIntyre
Fifth Supervisor
John Campbell
Abstract
Preclinical studies have demonstrated that exercise and dietary restriction enhance antitumour immunity and synergize with chemotherapy, yet clinical translation remains limited. This thesis combines narrative and systematic reviews with two clinical investigations to examine whether exercise medicine and dietary restriction in the form of fasting can modulate systemic immune profiles during (neo)adjuvant chemotherapy (with or without immunotherapy), with a focus on women with early-stage breast cancer.
The narrative review in Chapter 2 established the conceptual foundation for this work by outlining how chemotherapy efficacy partly depends on antitumour immune responses, and how dietary restriction and exercise appear to enhance immune competence and potentiate chemotherapy in preclinical models and emerging clinical studies. Chapter 3 extended this rationale through a systematic review of clinical trials evaluating exercise, diet, and combined interventions during chemotherapy, identifying limited but encouraging effects on tumour response and survival, and emphasizing the need for rigorous trials with clinical endpoints.
Two exploratory clinical investigations assessed the feasibility and preliminary immunological effects in women undergoing (immuno)chemotherapy. The FASTEX pilot study was a non-randomised investigation of two separate interventions: a supervised aerobic and resistance exercise program and a fasting-mimicking diet (FMD), each compared with a shared convenience control group that consented to provide blood samples only. The 12-week exercise program was feasible, with 11 of the 13 participants recruited completing the intervention with high attendance and adherence rates and no serious adverse events. Exercise promoted a more terminally differentiated T-cell phenotype, particularly in CD8+ T cells, characterised by expansion of CD8+ EMRA subsets and reduced naïve T-cell frequencies, as well as signals toward increased proportions of CD57 and PD-1 expressing CD8+ T cells relative to controls, while controls showed a signal toward a greater rise in CD56bright CD16+ NK cells. Exercisers appeared to mitigate the insulin rise observed in controls. In addition, participants in the exercise group maintained lean mass, prevented fat mass gain, and reported improved quality of life at the end of the intervention.
The FMD case series demonstrated lack of feasibility, with only five participants enrolling and only two of five participants completing at least one FMD cycle. Moreover, for one of the cases, post-intervention assessments were significantly delayed due to serious treatment-related adverse events, which challenged the interpretation of the outcomes. For the two patients, exploratory immune and metabolic changes were observed, including shifts toward terminally differentiated CD8+ EMRA T cells and lower proportion of naïve T cells, as well as higher proportion of HLA-DR and PD-1 expressing T cells compared to control patients. Metabolically, glucose and insulin remained stable and IGFBP-1 increased in one case, contrasting with modest rises in controls. Body composition responses diverged, with one case showing improved fat and lean mass profiles and the other demonstrating fat and visceral gains with loss of appendicular lean mass. Both participants reported declining quality of life and increasing fatigue.
These findings from the FASTEX trial remain preliminary and hypothesis-generating due to substantial variability in blood sampling relative to chemotherapy infusions among patients and the small sample size, and therefore require confirmation in larger, better-designed studies.
Overall, this thesis integrates mechanistic evidence with preliminary clinical observations, indicating that exercise, and potentially fasting, may modulate systemic immunity during chemotherapy. Two additional narrative reviews on precision exercise and precision nutrition (presented in Part II of this thesis) outline future directions for personalised interventions tailored to tumour- and patient-specific characteristics to optimise treatment efficacy and prognosis in breast cancer.
Access Note
Access to appendices B3 & B4 of this thesis is not available
Access to this thesis is embargoed until 13th June 2027
Recommended Citation
Crespo Garcia, C. (2026). Exercise and fasting as adjuvant therapies in the treatment of patients with early-stage breast cancer. Edith Cowan University. https://doi.org/10.25958/esc3-mx21