Breast Cancer, Breast Neoplasms
Conditions
Keywords
Breast Cancer, Neoadjuvant Therapy, Neoadjuvant Chemotherapy, Exercise, Exercise Therapy, Physiotherapy, MicroRNA, Biomarkers, Translational Research, Precision Oncology, Patient-Reported Outcomes, Pathological Complete Response, Quality of Life, Supportive Care
Brief summary
The goal of this clinical trial is to learn whether a physiotherapy-led exercise programme delivered during treatment before surgery (neoadjuvant therapy) for breast cancer can improve physical fitness, quality of life, and how well people cope with treatment. The study will also investigate whether blood and tumour markers, including microRNAs (small molecules that help regulate gene activity), together with information about the participant and the cancer itself (clinical information), can help predict how well patients respond to treatment. The main questions this study aims to answer are: * Does a structured physiotherapy-led exercise programme improve physical fitness, muscle strength, quality of life, and the ability to complete treatment? * Can blood and tumour markers, together with clinical information, help predict which patients will have the best response to treatment? Researchers will compare participants who receive the physiotherapy-led exercise programme with participants who receive standard care to determine whether the exercise programme improves physical and patient-reported outcomes. Participants will: * Receive standard treatment before surgery for breast cancer. * Be randomly assigned to either a 14-week physiotherapy-led personalised exercise programme or standard care. * Provide blood and tumour tissue samples for research. * Complete physical assessments and questionnaires about their symptoms, physical function, and quality of life during treatment. * Be followed throughout treatment, surgery, and follow-up to assess treatment response and other health outcomes.
Detailed description
Breast cancer is a heterogeneous disease with substantial variability in response to neoadjuvant systemic therapy despite advances in systemic treatment. Although pathological complete response (pCR) is an established surrogate marker of treatment efficacy in selected breast cancer subtypes, there remains a need for improved molecular and clinical predictors of treatment response, disease progression, and long-term outcomes. Circulating and tumour-derived microRNAs (miRNAs) have emerged as promising translational biomarkers because of their biological stability and potential to reflect tumour biology and dynamic changes during therapy. The IRELAND Trial is designed to prospectively integrate molecular, clinical, imaging, physiological, and patient-reported data collected throughout the neoadjuvant treatment pathway. The study aims to develop a comprehensive understanding of factors associated with treatment response and patient outcomes by combining biological specimen analysis with longitudinal clinical assessment. Blood and tumour tissue specimens will be collected at predefined time points for translational analyses, while radiological, pathological, and patient-reported outcome data will be collected prospectively using standardised assessment methods. Embedded within the translational cohort is a randomised controlled trial (CanReAct Trial) evaluating a structured 14-week physiotherapist-led personalised adaptive exercise programme delivered concurrently with standard-of-care neoadjuvant systemic therapy. Participants will be randomised to receive either the exercise intervention or standard care. The intervention is intended to optimise physical function during treatment and evaluate its effects on functional capacity, treatment tolerance, quality of life, and other patient-centred outcomes without altering oncological management. By integrating translational biomarker research with a structured supportive care intervention, the IRELAND Trial seeks to generate evidence that may improve prediction of treatment response while informing future personalised management strategies for patients undergoing neoadjuvant therapy for breast cancer.
Interventions
BEHAVIORALPhysiotherapist-Led Personalised Adaptive Exercise Programme
A structured 14-week physiotherapist-led personalised adaptive exercise programme delivered concurrently with standard neoadjuvant systemic therapy. The intervention includes supervised and home-based aerobic and resistance exercise with progression tailored according to participant fitness, treatment tolerance and clinical status.
Sponsors
National University of Ireland, Galway, Ireland
Galway University Hospitals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
Participants will be randomised in a 1:1 ratio to either a structured 14-week physiotherapist-led personalised adaptive exercise programme delivered concurrently with neoadjuvant systemic therapy or standard care. Randomisation applies solely to the structured physiotherapy intervention and will not modify oncological treatment decisions.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or older. 2. Histologically confirmed diagnosis of breast cancer. 3. Planned treatment with standard-of-care neoadjuvant systemic therapy. 4. Ability to provide written informed consent. 5. Ability to partake in 14-week physiotherapist-led personalised adaptive exercise programme. 6. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2.
Exclusion criteria
1. Inability to provide informed consent. 2. Inability to complete patient-reported outcome assessments. 3. Pregnancy. 4. Presence of any condition that, in the opinion of the treating clinician, would preclude participation in study procedures. 5. Inability to partake in 14-week physiotherapist-led personalised adaptive exercise programme.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response (pCR) | At definitive surgery following completion of neoadjuvant systemic therapy | Pathological complete response (pCR), defined as the absence of residual invasive cancer in the breast and axillary lymph nodes at definitive surgery following completion of neoadjuvant systemic therapy. |
| Estimated VO2max | Baseline and 14 weeks (end of intervention) | Change in aerobic capacity (i.e. VO2max) as estimated from 6 minute walk test, following the physiotherapist-led intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle endurance (upper body) | Baseline and Week 14 | Change in muscle endurance measured using a push up test (as many correctly performed push ups in a row as possible). |
| Participant retention rate | Throughout the 14-week intervention | Proportion of enrolled participants who complete the 14-week physiotherapist-led exercise programme and remain in the study until completion of the intervention. |
| Adherence | Throughout the 14-week intervention | Adherence to the physiotherapy intervention assessed by attendance rate and exercise log compliance. |
| Exercise-related adverse events | Throughout the 14-week intervention | Incidence and severity of adverse events attributable to the exercise intervention. |
| Disease-free survival | Up to 10 years after surgery (or according to study follow-up) | Time from surgery to disease recurrence or death from any cause. |
| Circulating and tumour microRNA expression | Baseline, start of Cycle 3 chemotherapy, after completion of the 14-week physiotherapy programme, at surgery, 4 weeks post-surgery, and 12 months post-surgery (each cycle is 2-4 weeks). | Identification of circulating and tumour microRNA expression profiles associated with pathological and radiological response to neoadjuvant therapy. |
| Longitudinal circulating microRNA expression | Baseline, start of Cycle 3 chemotherapy, after completion of the 14-week physiotherapy programme, at surgery, 4 weeks post-surgery, and 12 months post-surgery (each cycle is 2-4 weeks). | Longitudinal changes in circulating microRNA expression during neoadjuvant therapy and follow-up. |
| MicroRNA expression: Clinicopathological associations | After completion of 12-month post-surgery follow-up. | Associations between microRNA expression profiles and clinicopathological characteristics, including tumour subtype, stage, hormone receptor status, HER2 status and treatment variables. |
| MicroRNA expression: Genomic and radiomic correlations | After completion of 12-month post-surgery follow-up. | Correlation of microRNA signatures with genomic recurrence scores and radiomic imaging features. |
| Lean body mass | Baseline and Week 14 | Change in lean body mass (kg) measured using body composition analysis. |
| Hydration | Baseline and Week 14 | Change in total body water (L) measured using body composition analysis |
| Fat mass | Baseline and Week 14 | Change in fat mass (kg) measured using body composition analysis. |
| Body weight | Baseline and Week 14 | Change in body weight, measured in kilograms (kg). |
| Body mass index | Baseline and Week 14 | Change in body mass index (BMI), calculated as weight in kilograms divided by height in metres squared (kg/m²). |
| Change in quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Baseline, start of Cycle 3 chemotherapy, after completion of the 14-week physiotherapy programme, at surgery, 4 weeks post-surgery, and 12 months post-surgery (each cycle is 2-4 weeks). | Change in quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Scores range from 0 to 100. For the Global Health Status/Quality of Life and functional scales, higher scores indicate better quality of life/functioning. For the symptom scales, higher scores indicate greater symptom burden (worse outcome). |
| Muscle Strength | Baseline and Week 14 | Change in muscle strength measured using estimated one-repetition maximum (1RM) between baseline and completion of the intervention. |
| Fatigue | Baseline and Week 14 | Change in fatigue assessed using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire. FACT-F is a patient-reported measure of cancer-related fatigue. Total scores range from 0 to 52, with higher scores indicating less fatigue (i.e. better outcome). |
| Change in quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module 45 (EORTC QLQ-BR45) | Baseline, start of Cycle 3 chemotherapy, after completion of the 14-week physiotherapy programme, at surgery, 4 weeks post-surgery, and 12 months post-surgery (each cycle is 2-4 weeks). | Change in quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module 45 (EORTC QLQ-BR45). Scores range from 0 to 100. For the functional scales, higher scores indicate better functioning. For the symptom scales, higher scores indicate greater symptom burden (worse outcome). |
| Muscle endurance (lower body) | Baseline and Week 14 | Change in muscle endurance measured using a squat test (as many squats as possible in one minute). |
Contacts
CONTACTEoin P Kerin, MB BCh BAO MCh
CONTACTLuis Bouz Mkabaah, MB BCh BAO MCh
PRINCIPAL_INVESTIGATORMichael J Kerin, MB BCh BAO MCh DSc
University of Galway
Outcome results
None listed