OptiTrain - Optimal Training Women With Breast Cancer
Condition: Well Being
MeSH terms: Breast Neoplasms
Study type: Interventional

Summary: 
      This study on women with breast cancer during and after chemo- and hormonal therapy compares
      the effect of different physical training programs on physical and mental well-being and
      systemic inflammation mechanisms in blood. In a sub-group of participants, mitochondrial
      biogenesis and function and other molecular processes in skeletal muscle biopsies are
      studied. The women will be randomly allocated into three different intervention arms, a
      control arm with usual care and two different training arms. All participants will respond to
      questionnaires and have blood samples and taken and for a subgroup muscle biopsies before and
      after the exercise intervention. Participants will be supported to uphold exercise through
      collaboration with Friskis & Svettis and followed for 5 years. Some of the women will also be
      asked to participate in an in depth interview about the experiences of exercise during
      ongoing treatment. This study will contribute to increased knowledge about the type,
      intensity and frequency of training that patients with breast cancer benefit most from with
      regards to impact on physical and mental wellbeing. This knowledge is of great importance
      since experience shows that patients and relatives often seek information about
      rehabilitation, self-care and physical activity. The study will also contribute to the
      improvement of the patients´ quality of life, ability to return to work, and reduce social
      costs, but above all, increase the possibility for development and implementation of
      evidence-based rehabilitation of women with breast cancer during and after active treatment.
    

Detailed description: 
      Purpose The main aim is to, in women undergoing chemotherapy for breast cancer, explore how
      different training interventions impact physical capacity and psychological well being.

      Research questions

        -  Does PA improve the ability to return to work after breast cancer treatment is
           completed?

        -  How do women with breast cancer during chemotherapy treatment respond to controlled and
           supervised aerobic fitness training and a combination of aerobic fitness training and
           strength training in physiological, structural and molecular outcome measures such as
           muscular strength, aerobic fitness, muscle mass, mitochondrial density, gene activity in
           muscle and B-Hb, s-CRP and other blood variables,?

        -  Is there a difference between the women in the aerobic exercise training group, the
           combined aerobic and strength-training group and the control group regarding symptom
           distress and health related quality of life?

        -  Are there any effects of exercise training on chemotherapy completion and
           hospitalization rates?

        -  Is adherence to physical exercise impacted by the individuals' personality?

        -  Are there any remaining effects of the physical exercise intervention, on
           cardiotoxicity, cognitive function, survival and morbidity, up to 5 years after
           treatment is completed?

        -  Is the intervention cost-effective?

      Study design and methods Participants A total of 240 women will be recruited from the
      Department of Oncology Breast and Sarcoma units at Radiumhemmet and Södersjukhuset,
      Karolinska University Hospital.

      Inclusion criteria: patients up to 70 years with breast cancer Stage I-IIIa before the start
      of chemotherapy. Exclusion criteria: patients with advanced disease, patients where physical
      activity is considered contraindicated because of medical reasons such as heart or lung
      disease, brain or bone metastases, cognitive dysfunction, and patients who do not speak or
      understand the Swedish language.

      Randomization The Clinical Trials Unit (KPE) at Radiumhemmet, Karolinska
      Universitetssjukhuset, conducts inclusion to the study and randomization. The participants
      are allocated to either two different training groups or a control group. The participants
      are also randomized to a muscle biopsy (n=45) before and after the intervention.

      Group 1) includes strength training of the large muscle groups (2-3 sets, 8-12 repetitions on
      an intensity of 80 % of 1-RM) and 3x3 min high intensity aerobic exercise (16-18 on Borg
      scale) on an exercise bike or treadmill twice a week for 16 weeks.

      Group 2) includes aerobic exercise on an exercise bike or treadmill, 20 min of moderate
      intensity (13-15 on Borg scale), and 3x3 min high intensity aerobic exercise (16-18 on Borg
      scale) twice a week during 16 weeks.

      Group 3) control group, will get standard information around physical activity during
      treatment but no supervised training.

      Data Collection Data will be collected for all study participants regarding demographics and
      diagnosis, cancer treatment, laboratory and sick leave data (patient-reported), relapse,
      survival, co-morbidity and cause of death in relevant registers.

        -  Data collection of demographic data occurs before (before randomization) and after the
           intervention, and at three time points: 1 year, 2 years and 5 years after treatment is
           completed. Baseline is about 5 weeks after surgery and before initiation of
           chemotherapy.

        -  All participants that accept participation in the study will undergo a resting ECG
           examination and will provide responses to a small, targeted set of heart disease history
           questions.

        -  Muscular strength is measured with the instrument JAMAR that is a dynamometer, measuring
           muscle strength in the hand. Lower limb muscle strength is measured through isometric
           mid-thigh pull. This is assessed in all study participants at all time points: before
           and the intervention, year 1, 2, and 5.. The instruments have good reliability and
           validity.

        -  Before and after the intervention aerobic fitness (VO2-max) of the participants in the
           intervention groups will be assessed with a submaximal exercise test. This will be
           measured at all time points: before and the intervention, year 1, 2, and 5.

        -  Algometry, to measure pain sensitivity will be performed at time points: before and
           after the intervention, year 2 and 5.

        -  Chemotherapy completion, hospitalization, hemoglobin-, lymphocyte- and platelet
           concentrations during chemotherapy will be extracted from the patients' medical records.

        -  Blood sampling and muscle biopsy procedures will take place at the KPE lab Radiumhemmet,
           Karolinska University Hospital, Solna. Muscle biopsies will be obtained under local
           anesthesia in the m. vastus lateralis (approximately 100 mg) with a Bergström needle.
           This takes place before the intervention starts and 48-72 hours after the last training
           session. Mitochondrial density and muscle morphology will be analyzed. Venous blood is
           sampled at time points: before and the intervention, year 1, and 5, for analysis of
           white cell distribution, for markers of systemic inflammation, and markers of cardiac
           damage

        -  Physical activity level and energy consumption is determined by ActiGraph GT3X
           (Actigraph). Actigraph is a combined heart rate sensor and accelerometer that
           continuously collects data. The method has been previously tested and is shown to have
           good reliability and validity. In this project all the participants in the three groups
           will be carrying an Actigraph for seven days, before the intervention. An Activity Diary
           for daily subjective reporting of physical activity will also be used during the
           intervention period.

      Instruments

        -  Piper Fatigue Scale assesses fatigue in four dimensions. The scale has been shown to
           have psychometric properties that are reliable for assessing subjective dimensions of
           fatigue among Swedish populations of cancer patients. Data will be collected for all
           study participants (intervention and control) before randomization and after the
           intervention, and at 1 year, 2 years and 5 years after treatment.

        -  Memorial Symptom Assessment Scale (MSAS) assesses 32 common cancer-related symptoms. The
           instrument is validated for Swedish patients with breast cancer. Data will be collected
           for all study participants before randomization and after the intervention, and at 1
           year, 2 years and 5 years after treatment.

        -  EORTC QLQ-C30 is a cancer-specific instrument that measures health-related quality of
           life in terms of physical, emotional, social, cognitive and everyday function. Data will
           be collected for all study participants before randomization and after the intervention,
           and at 1 year, 2 years and 5 years after treatment.

        -  Sense of coherence (SOC) is a questionnaire, which shows how a person sees the world and
           his own life as comprehensible, manageable and meaningful. Individuals with a strong
           sense of coherence are able to mobilize the resources to manage their health during
           illness and treatment. SOC short version consists of l3 questions that all participants
           complete once before the start of treatment. The Swedish version of the SOC-13 has been
           shown to have good validity and reliability. It has also demonstrated high internal
           consistency.

        -  The Amsterdam Cognition Scan- an online neuropsychological test battery that measures a
           broad variety of cognitive functions, measured five years following inclusion to the
           exercise intervention

        -  Echocardiogram- to measure cardiac function, five years following inclusion to the
           exercise intervention

      Qualitative interviews

      • Individual interviews about/around the experience of physical activity associated with
      chemotherapy treatment will be carried out with 15 participants. An open question will be
      asked, such as "Can you describe how you experienced the period of training?". Because of the
      nature of this question, the women will have the freedom to narrate their stories, and the
      interview will focus on elements that surface as significant. Supplementary questions will be
      asked to create depth and further understanding of the phenomena.

      Data Analysis Muscle and blood analysis: From 45 participants in the project, we plan to take
      a muscle biopsy before and after the training intervention. The molecular exercise physiology
      lab is fully equipped to store muscle biopsies and other biological material. Many methods
      are set-up in our muscle lab and others are performed in different core facilities. Molecular
      and biochemical analyses: Skeletal muscle biopsy samples are obtained with the percutaneous
      needle technique. Analysis of protein content, CS activity, and immunohistochemistry will be
      performed.

      Quantitative Collected quantitative data will be analysed using parametric statistics for
      normally distributed data and non-parametric statistics for non-normally distributed data.
      Subgroup analysis will be conducted with a focus on the type of treatment. Power Calculation:
      variable cancer related fatigue, selected significance level 0.05, power 0.80 = 240 patients
      will be recruited in total to detect a statistical difference with medium effect size.

      Qualitative Qualitative data from individual interviews with 15 patients will be analyzed
      inductive with content analysis.

      Workplan Data collection is currently ongoing and 80 patients are included in the study. With
      the current inclusion rate the 240 participants will be included by the end of 2015.

      To support the women to uphold PA after treatment is completed a collaboration has been
      initiated with Friskis & Svettis in Stockholm, during the five year follow up period this
      will encompass FaR (physical activitiy receipt) and invitations to motivational healthy life
      style sessions three times a year, the sessions will also include information on longterm
      effects/symptoms of treatment and support with self care.
    

Intervention name(s): Resistance and aerobic training; Aerobic training; Standard supportive care
Intervention type(s): Other; Other; Other
Intervention description(s): Group 1) includes strength exercise of the large muscle groups (2-3 sets, 8-12 repetitions on an intensity of 80 % of 1-RM) and 3x3 min high intensity aerobic exercise (16-18 on Borg scale) on an exercise bike or treadmill twice a week for 16 weeks; Group 2) includes aerobic exercise on an exercise bike or treadmill, 20 min moderate intensity (13-15 on Borg scale), and 3x3 min high intensity (16-18 on Borg scale) twice a week during 16 weeks; Standard supportive care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Breast cancer, chemotherapy, symptoms, optimal training