Exercise Interventions for Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

Study Overview
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Brief Summary
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The BENEFIT-Study is a randomized controlled 3-arm intervention trial investigating the currently discussed hypothesis that exercise concomitant to chemotherapy (CTx) may have a beneficial effect on cancer prognosis by boosting the anti-tumoral effect of the cytostatics or by enhancing therapy compliance. This hypothesis is based on pre-clinical and exploratory clinical trials. Breast cancer patients scheduled for neoadjuvant CTx will be randomized to either a resistance training or an aerobic training concomitant to the neoadjuvant CTx, or a waiting list control group that will get no exercise intervention during neoadjuvant CTx (i.e. usual care) but will exercise after breast surgery. The primary study endpoint is the tumor size. Further, the effects of resistance and aerobic exercise on the clinical-pathologic stage (CPS-EG) score, the pathological complete response (pCR), tolerability and compliance to CTx, physical fitness, patient reported outcomes such as fatigue, sleep problems, quality of life, depressive symptoms, anxiety and pain, as well as cognitive function, and selected biomarkers will be investigated. A confirmation of the study hypothesis would be a strong argument for patients to engage in exercise as early as during neoadjuvant CTx. The trial will also provide evidence-based guidance for patients regarding type and timing of training.

Official Title
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A Randomized 3-arm Exercise Intervention Trial for Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: Resistance exercise
* Other: Aerobic exercise
* Other: Usual care during neoadjuvant chemotherapy/Exercise after surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women ≥ 18 years of Age Unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy Scheduled for neoadjuvant CTx (but not yet started) Confirmed hormone receptor and Her2 status Sufficient German language skills Willing to train at the exercise facilities twice per week Exclusion Criteria: Any physical or mental conditions that would hamper the adherence to the training programs or the completion of the study procedures Engaging in systematic intense exercise training (at least 1h twice per week)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Resistance exercise<br> | Other: Resistance exercise<br>* The training will take place twice weekly over the course of neoadjuvant CTx at the NCT Heidelberg or in regional qualified centers under supervision and guidance of experienced exercise therapists. The progressive resistance exercise comprises 8 machine-based exercises, each performed in 3 sets, 12 repetitions at 60-80% of one repetition maximum (1-RM).<br>|
| Active Comparator: Aerobic exercise<br> | Other: Aerobic exercise<br>* The training will take place twice weekly over the course of neoadjuvant CTx at the NCT Heidelberg or in regional qualified centers under supervision and guidance of experienced exercise therapists. The aerobic exercise will be performed on a cycle ergometer (or alternatively at a treadmill, elliptical, rowing ergometer, or combination) progressing from 60% to 70% VO2max with increasing duration. During weeks 7-18 the goal is to perform an extensive interval training.<br>|
| Other: Waitlist control<br> | Other: Usual care during neoadjuvant chemotherapy/Exercise after surgery<br>* The control group receives no exercise intervention during neoadjuvant CTx, which reflects the usual care condition. To investigate effects of different exercise timing, and to provide those patients also a potential health benefit and reduce drop-out and contamination, the control group will receive 18 weeks resistance or aerobic exercise (according to their personal preferences) after breast cancer surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor size | percentage of change from the maximal diameter of the lesion assessed before neoadjuvant chemotherapy (by mammography or sonography) to the maximal diameter of the tumor assessed after neoadjuvant chemotherapy at breast surgery | change from baseline (before start of neoadjuvant chemotherapy) to breast surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CPS-EG score | The Clinical-Pathologic Stage (CPS-EG) score combines clinical tumor stage prior to neoadjuvant therapy (CS), pathological tumor stage after neoadjuvant treatment (PS), estrogen receptor status (E) and grading (G). It has been shown to be a valid prognostic factor to discriminate among patient subgroups with respect to survival after neoadjuvant CTx. | at breast surgery | 
| pCR | The Pathological Complete Response (pCR) is defined as ypT0/is ypN0 and has been consistently demonstrated to be a good prognostic factor for long-term benefit from neoadjuvant CTx. | at breast surgery | 
| Fatigue Assessment Questionnaire (FAQ) | Validated 20-item multidimensional self-assessment questionnaire to assess the physical, affective, and cognitive dimension of cancer-related fatigue | at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery | 
| EORTC QLQ-C30 / BR23 | Validated 30-item self-assessment questionnaire to assess quality of life aspects. | at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery | 
| Patient Health Questionnaire for Depression and Anxiety (PHQ-4) | A validated 4-item screener for depression and anxiety. | at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery | 
| Pittsburgh Sleep Quality Index (PSQI) | Validated questionnaire to assess sleep quality and sleep problems. | at baseline, week 9, post-chemotherapy (before breast surgery); months 6 and 12 after breast surgery | 
| Spiroergometry (VO2max) |  | at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery | 
| Isometric and isokinetic muscle strength measured by ISOMED 2000 |  | at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery | 
| Body mass index |  | at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery | 
| Self-developed physical activity questionnaire including type, duration, frequency and intensity of sports, cycling,and walking |  | Follow-up (6 months and 12 months after breast surgery) | 
| Cognitive function - HVLT-R | Hopkins Verbal Learning Test - Revised (HVLT-R) | at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery | 
| Cognitive function - TMT | Trail Making Test | at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery | 
| Cognitive function - COWA | Controlled Oral Word Association | at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery | 
| Sleep quality | Measured with ActiGraph (accelerometry) | at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery | 
| Sleep efficiency | Measured with ActiGraph (accelerometry) | at baseline, post-chemotherapy (before breast surgery); month 6 after breast surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise, resistance training, aerobic training, breast cancer, neoadjuvant chemotherapy, fatigue, quality of life, tumor response