Feasibility of exercise to improve insulin sensitivity in postmenopausal women who are overweight or obese receiving chemotherapy for breast cancer

INTERVENTION: Randomisation: Block randomization will be performed using a computer‐generated random number list (e.g., https://www.randomization.com) with a 2:1 allocation using random block sizes of 2 and 4 by an independent researcher. As the researchers are primarily interested in feasibility and acceptability, a 2:1 ratio to the active intervention compared to the control arm will provide more data to inform the feasibility and acceptability of the active intervention, whilst still allowing for an estimate of the effect size and outcome variability which can be used to inform a sample size calculation in the subsequent confirmatory trial. Allocating our sample of 40 participants at a 2:1 ratio results in 27 participants allocated to the intervention arm and 13 allocated to the standard care arm. The allocation sequence will be concealed from the researcher (HS) enrolling and assessing participants in sequentially numbered, opaque, sealed and stapled envelopes. Aluminium foil inside the envelope will be used to render the envelope impermeable to intense light. To prevent subversion of the allocation sequence, the name and date of birth of the participant will be written on the envelope by the independent researcher. Corresponding envelopes will be opened by the PhD researcher (HS) only after the enrolled participants complete all baseline assessments and it is time to allocate the intervention. Intervention: Participants assigned to the exercise group will be required to attend 28 in‐person sessions (initial visit, acute exercise session, a post‐acute exercise home‐based assessment, 24 supervised exercise sessions, and a final assessment visit) as well as 12 unsupervised home‐based exercise sessions. Acute exercise intervention: Patients randomly assigned to the exercise arm w CONDITION: Insulin sensitivity in overweight/obese postmenopausal women receiving chemotherapy for breast cancer ; Nutritional, Metabolic, Endocrine PRIMARY OUTCOME: Feasibility as assessed by recruitment rate (40 patients in 12 months), retention rate (at least 70%), and adherence to exercise (at least 67% of sessions completed) SECONDARY OUTCOME: 1. Exercise compliance measures recorded by exercise supervisors from commencement and completion of the 12‐week exercise intervention.; 2. Insulin sensitivity measured using an oral glucose tolerance test at baseline, post‐acute exercise, and post‐12‐week intervention testing via blood sampling (baseline and 12‐week follow‐up only) and continunous glucose monitoring (all timepoints).; 3. Pro‐ and anti‐inflammatory cytokines measured using multiple Xcytokine assay kits (including interleukin 6 (IL‐6), IL‐4, IL‐10, IL‐12p70, TNF‐a and IFN‐g) and adipokines (adiponectin, leptin and visfatin) using Lumine Xplatform. Oestrogen (Quantikine, R&D Systems Inc., Abingdon, UK) and C‐reactive protein (CRP) levels (Enzo Life Sciences, UK): Commercially available enzyme‐linked immunosorbent assays (ELISA). All measured at baseline, post‐acute exercise, and post‐12‐week intervention testing.; 4. Anthropometric measures: body mass inde X(via measured height and mass), body fat and fat‐free mass (via bioelectrical impedance), and measured waist circumference. Measured at baseline and post‐12‐week intervention testing.; 5. Physical function tests: cardiopulmonary fitness (via a ventilatory threshold treadmill test with gas analysis), muscular strength (via a 10‐repetition maximum chest press and leg press test). Measured at baseline and post‐12‐week intervention testing.; 6. Quality of life measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORCT‐QLQ‐C30) questionnaire and its breast‐specific (BR23) subscale. Measured at baseline and post‐12‐week intervention testing.; 7. Treatment‐related outcomes: chemotherapy‐related adverse events, dose‐limiting toxicity, time to toxicity, relative dose intensity, and chemotherapy discontinuation, termination, modifications, or delays. Adverse events (AE) will be graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (v5.0). Measured from baseline to completion of post‐12‐week intervention testing.; 8. Patients’ satisfaction and acceptability obtained by conducting qualitative semi‐structured interviews conducted 1 week following post‐12‐week intervention period with 15 patients chosen at random from the intervention group regardless of exercise intervention adherence.; 9. Physical activity patterns objectively measured using Withings HR Steel watches during the study period; 10. Exercise safety assessed by reporting exercise‐related adverse events after the acute exercise bout and at the beginning of each supervised exercise session INCLUSION CRITERIA: 1. Females who are postmenopausal (not experiencing menstrual periods for the previous 12 months via self‐report) and aged between 45 and 69 years: as determined by self‐report. Participants will be asked to answer whether they are pre‐, peri‐, or post‐menopausal. If they have answered ‘post‐menopausal’, they will be asked to recall when their final menstrual cycle was. 2. Diagnosed with stage I‐III breast cancer with an ECOG performance status grade of 0‐2 as deemed by the oncology team at the time of diagnosis. 3. Have a body mass inde X(BMI) of 25 to 39.9 (i.e., overweight, or obese) kg/m2, or if Asian or South Asian a BMI of 23 to 39.9 kg.m2, respectively. BMI will be taken from patient notes. 4. Scheduled to undergo chemotherapy treatment for breast cancer under oncology supervision: determined by the oncology team. 5. No medical conditions prohibiting exercise as deemed by the oncologist. 6. Not engaging in regular exercise (i.e., meeting curren