Physical Exercise During Preoperative Chemotherapy for Breast Cancer

Study Overview
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Brief Summary
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Neoadjuvant chemotherapy (NACT) is increasingly used in breast cancer. The best proof of NACT efficacy is pathological complete response (pCR), i.e. the absence of invasive tumour on post-NACT surgical histopathology. While it is known that physical exercise can help patients to better tolerate and complete often harsh cancer treatments, it is an emerging area of research to understand if and how exercise exerts anti-tumour effects and improves oncological outcomes. The main aim of the Neo-ACT trial is to examine if a physical exercise intervention during NACT can increase pCR rates in breast cancer. Secondary aims are residual cancer burden, radiological tumour response, patient-related outcomes (health-related quality of life, physical activity), physiological outcomes (muscle strength, cardiorespiratory fitness), cancer treatment-related toxicities (cognitive dysfunction, chemotherapy completion rates) and long-term sick leave. Furthermore, the trial will explore how physical exercise affects anti-tumoral mechanisms inherent to therapy or host by hypothesis-generating translational analyses. 712 patients with primary invasive breast cancer will be randomized to either a supervised intervention of high-intensity interval and resistance training during NACT, supported by an exercise app, or to usual care, and followed for two years. Physical activity is meticulously tracked. By offering patients active involvement, the trial contributes strongly to the concept of personalized medicine.

Detailed Description
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The Neo-ACT assesses the primary endpoint pathological complete response (pCR) and the secondary endpoints Residual Cancer Burden (RCB), objective tumour response (RECIST), all-cause, breast cancer-specific, and recurrence-free survival at 2, 5 and 10 years, health-related quality of life assessed by the EORTC QLQ-C30 and BR23 questionnaires, self-reported physical activity (Modified Godin Leisure Time Physical activity questionnaire), toxicity-related outcomes (chemotherapy completion rates, number of unplanned hospital admissions during NACT, objective cognitive dysfunction (Amsterdam Cognition Scan), cardiac toxicity and sick leave), device-measured physical activity level (Fitbit activity tracker), muscle strength (handgrip strength test and hypothetical 1-RM maximal leg muscle strength tests), and cardiorespiratory fitness (Ekblom-Bak submaximal cycle test). Participants randomized to the exercise group will complete 120 min exercise sessions per week from initiation of NACT to surgery (approx. five months): Progressive home exercise program by an individualised mobile phone application, supported by local physiotherapists Initial exercise intensity individually tailored to each patient's fitness at baseline and rate of perceived exertion during the program and adapted if required Sessions will begin with a 3-minute moderate intensity (12-13 on Borg's Rate of Perceived Exertion (RPE) scale) warm-up.

Official Title
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Physical Exercise During Neoadjuvant Chemotherapy for Breast Cancer as a Means to Increase Pathological Complete Response Rates: the Randomized Neo-ACT Trial

Conditions
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Breast Cancer

Intervention / Treatment
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* Behavioral: Physical training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with primary invasive breast cancer cT1-T3 cN0-2 Full tumour biology available before initiation of NACT Oral and written consent Age ≥ 18 years Able to travel to the exercise testing and training premises Anticipates being able to adhere to the exercise program requirements Exclusion Criteria: Pregnancy or breast-feeding Inability to absorb or understand the meaning of the study The presence of musculoskeletal, neurological, respiratory, metabolic or cardiovascular conditions that may prevent safe completion of the exercise demands of the study Currently performing equal to or more than 150 mins of moderate to high intensity aerobic exercise and 2 sessions per week of moderate intensity resistance exercise

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomization to supervised high-intensity interval training during neoadjuvant chemotherapy or usual information about physical activity.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard<br>Routine information on the benefit of physical activity | |
| Experimental: Intervention<br>High-intensity interval and strength training during neoadjuvant chemotherapy | Behavioral: Physical training<br>* Participants randomized to the exercise group will complete two structured 60-min exercise sessions per week from initiation of NACT to surgery (approx. five months).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response | Absence of residual invasive tumor in breast and axilla at surgery | 5-6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global health-related quality of life | assessed by the EORTC QLQ-C30 questionnaire | baseline, after 1 and 2 years | 
| Breast cancer-related quality of life | assessed by the EORTC QLQ-B23 questionnaire | baseline, after 1 and 2 years | 
| Self-reported physical activity | Modified Godin Leisure Time Physical activity questionnaire | baseline, pre-surgery, 1- and 2-year follow-up | 
| Chemotherapy completion rate | proportion of participants receiving the planned number of treatments | 1 year | 
| Cumulative chemotherapy dosage | total dose of NACT received to account for potential dose reduction | 1 year | 
| Objective cognitive dysfunction | online neuropsychological test (Amsterdam Cognition Scan) | baseline and 1 year | 
| Sick leave | Patient-reported absence from work | pre-surgery and at 1- and 2-year follow-up | 
| Device-measured physical activity level | Fit-bit tracker | baseline and 5-6months (pre surgery) | 
| Muscle strength | hypothetical 1-RM maximal leg muscle strength test | baseline and 5-6 months | 
| Handgrip strength | handgrip strength test | baseline and 5-6 months | 
| Cardiorespiratory fitness | Åstrand submaximal cycle test | baseline and 5-6 months (pre-surgery) | 
| Radiological tumour response | RECIST | 5-6 months | 
| Residual Cancer Burden (RCB) | Degree of tumor response to NACT | 5-6 months |