IRELAND Trial: A Translational Biomarker and Exercise Study During Neoadjuvant Breast Cancer Therapy (IRELAND)

August 28, 2026 updated by: Michael Kerin, National University of Ireland, Galway, Ireland

Investigating Molecular and Clinical pREdictors of Outcome foLlowing neoadjuvAnt Therapy in Breast caNcer Dynamics (IRELAND Trial): A Translational Study With an Embedded Physiotherapist-Led Exercise Randomised Controlled Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

250

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Physiotherapist-Led Exercise Programme
Participants allocated to the experimental arm will receive a structured 14-week physiotherapist-led personalised adaptive exercise programme delivered concurrently with standard neoadjuvant systemic therapy. The programme includes supervised and home-based aerobic and resistance exercise, with progression tailored to participant clinical status and treatment tolerance.
Behavioral: Physiotherapist-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.
No Intervention: Standard Care
Participants will receive standard neoadjuvant systemic therapy and routine clinical care without the structured physiotherapist-led exercise programme.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Estimated VO2max
Time Frame: 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
Baseline and 14 weeks (end of intervention)
Pathological complete response (pCR)
Time Frame: 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.
At definitive surgery following completion of neoadjuvant systemic therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Muscle Strength
Time Frame: Baseline and Week 14
Change in muscle strength measured using estimated one-repetition maximum (1RM) between baseline and completion of the intervention.
Baseline and Week 14
Fatigue
Time Frame: 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).
Baseline and Week 14
Muscle endurance (lower body)
Time Frame: Baseline and Week 14
Change in muscle endurance measured using a squat test (as many squats as possible in one minute).
Baseline and Week 14
Muscle endurance (upper body)
Time Frame: 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).
Baseline and Week 14
Participant retention rate
Time Frame: 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.
Throughout the 14-week intervention
Adherence
Time Frame: Throughout the 14-week intervention
Adherence to the physiotherapy intervention assessed by attendance rate and exercise log compliance.
Throughout the 14-week intervention
Exercise-related adverse events
Time Frame: Throughout the 14-week intervention
Incidence and severity of adverse events attributable to the exercise intervention.
Throughout the 14-week intervention
Disease-free survival
Time Frame: Up to 10 years after surgery (or according to study follow-up)
Time from surgery to disease recurrence or death from any cause.
Up to 10 years after surgery (or according to study follow-up)
Circulating and tumour microRNA expression
Time Frame: 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.
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 circulating microRNA expression
Time Frame: 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.
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).
MicroRNA expression: Clinicopathological associations
Time Frame: 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.
After completion of 12-month post-surgery follow-up.
MicroRNA expression: Genomic and radiomic correlations
Time Frame: After completion of 12-month post-surgery follow-up.
Correlation of microRNA signatures with genomic recurrence scores and radiomic imaging features.
After completion of 12-month post-surgery follow-up.
Lean body mass
Time Frame: Baseline and Week 14
Change in lean body mass (kg) measured using body composition analysis.
Baseline and Week 14
Hydration
Time Frame: Baseline and Week 14
Change in total body water (L) measured using body composition analysis
Baseline and Week 14
Fat mass
Time Frame: Baseline and Week 14
Change in fat mass (kg) measured using body composition analysis.
Baseline and Week 14
Body weight
Time Frame: Baseline and Week 14
Change in body weight, measured in kilograms (kg).
Baseline and Week 14
Body mass index
Time Frame: Baseline and Week 14
Change in body mass index (BMI), calculated as weight in kilograms divided by height in metres squared (kg/m²).
Baseline and Week 14
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)
Time Frame: 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).
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)
Time Frame: 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).
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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National University of Ireland, Galway, Ireland

Collaborators

Galway University Hospitals

Investigators

  • Principal Investigator: Michael J Kerin, MB BCh BAO MCh DSc, University of Galway

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 14, 2026

Primary Completion (Estimated)

November 1, 2028

Study Completion (Estimated)

August 1, 2029

Study Registration Dates

First Submitted

July 17, 2026

First Submitted That Met QC Criteria

August 28, 2026

First Posted (Actual)

September 2, 2026

Study Record Updates

Last Update Posted (Actual)

September 2, 2026

Last Update Submitted That Met QC Criteria

August 28, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRELAND
  • C.A. 3599 (Other Identifier: GUH Clinical Research Ethics Committee)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

The individual participant data (IPD) sharing plan has not yet been finalized. Any future data sharing will be considered in accordance with institutional policies, participant consent, applicable ethical approvals, and data protection regulations.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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