Aerobic Exercise, Resistance Exercise, or Flexibility and Relaxation Training in Inactive Older Female Breast Cancer Survivors
Condition: Breast Cancer; Cancer Survivor; Fatigue; Long-term Effects Secondary to Cancer Therapy in Adults; Psychosocial Effects of Cancer and Its Treatment
MeSH terms: Breast Neoplasms; Fatigue
Study type: Interventional

Summary: 
      RATIONALE: Aerobic exercise, resistance exercise, and flexibility and relaxation training may
      reduce fatigue and improve the health and quality of life of breast cancer survivors. It is
      not yet known which type of exercise is more effective for inactive older female breast
      cancer survivors.

      PURPOSE: This randomized clinical trial is studying aerobic exercise to see how well it works
      compared with resistance exercise or flexibility and relaxation training in improving the
      health and quality of life of inactive older female breast cancer survivors.
    

Detailed description: 
      OBJECTIVES:

      Primary:

        -  Compare the effects of aerobic exercise vs flexibility and relaxation training (control)
           on fatigue, aerobic capacity, functioning, and health outcomes in inactive older female
           breast cancer survivors.

        -  Compare the effects of resistance exercise vs flexibility and relaxation training
           (control) on fatigue, muscle strength, functioning, and health outcomes.

      Secondary:

        -  Compare the relative effects of aerobic exercise vs resistance exercise on fatigue,
           physical functioning, physical health, and mental health.

        -  Determine the mediating effects of fatigue and fitness on the relationship between
           exercise and physical functioning.

        -  Compare the individual and relative effects of aerobic exercise vs resistance exercise
           vs flexibility and relaxation training (control) on body composition and on biomarkers
           of cancer recurrence.

      OUTLINE: Patients are stratified according to current use of hormone manipulation therapy
      (none vs tamoxifen vs arimidex). Patients are randomized to 1 of 3 intervention arms.

        -  Arm I (progressive, aerobic exercise program): Patients undergo aerobic exercise
           training over approximately 45 minutes (not including warm-up or cool-down exercises) 3
           days a week for 18 months. During the first 12 months, patients attend supervised
           aerobic exercise sessions 2 days a week and complete 1 home-based aerobic exercise
           session using a modified exercise program designed by the investigative team. During the
           final 6 months, patients undergo aerobic exercise using an at-home program designed by
           the investigative team. Aerobic exercise training comprises simple stepping routines
           using benches of various heights while wearing a wrist monitor to record heart rate.
           Volume of aerobic exercise, determined by intensity (heart rate at percentage of heart
           rate reserve tailored to the patient) and duration (minutes in the target heart rate
           range), is gradually and progressively increased over the first 9 months of the exercise
           program. Exercise volume remains at a moderate level for the remainder of the program to
           provide an optimal physiologic challenge at a safe and tolerable level.

        -  Arm II (progressive, resistance exercise program): Patients undergo resistance exercise
           training 3 days a week for 18 months. During the first 12 months, patients attend
           supervised resistance exercise sessions 2 days a week and complete 1 home-based
           resistance exercise session using a modified exercise program designed by the
           investigative team. During the final 6 months, patients undergo resistance exercise
           using an at-home program designed by the investigative team. Resistance exercise
           training comprises the use of hand weights and barbells (for upper body resistance) and
           exercises in weighted vests (for lower body resistance). Patients wear a weighted vest
           while performing lower body strength training (chair rises, 90-degree squats, toe
           raises, forward lunges, lateral lunges). Patients use hand weights for upper body
           strength training (upright row, 1-arm row, overhead press, chest press, chest fly,
           biceps curl, triceps extension). Volume of strength training, determined by intensity
           (weight tailored to the patient) and duration (number of sets), is gradually increased
           from low weight and high number of repetitions to more weight and fewer repetitions over
           the first 6 months of the training period. Exercise volume remains at a moderate
           intensity for the remainder of the training period to provide an optimal physiologic
           challenge at a safe and tolerable level.

        -  Arm III (flexibility and relaxation training [control]): Patients perform a series of
           whole body flexibility (stretching) and relaxation (guided imagery, progressive
           neuromuscular relaxation, focused breathing) exercises 3 days a week for 18 months.
           During the first 12 months, patients attend supervised flexibility and relaxation
           exercise sessions 2 days a week and complete 1 home-based flexibility and relaxation
           exercise session using a modified exercise program designed by the investigative team.
           During the final 6 months, patients undergo flexibility and relaxation exercises using
           an at-home program designed by the investigative team.

      Muscle strength (measured by a one-repetition maximum test), aerobic capacity (measured by a
      6-minute walk test), functional arm strength (measured by grip dynamometer), physical
      functioning (measured by the Physical Performance Battery), flexibility (measured by the
      Chair Sit and Reach Test and the Back Scratch Test), balance (measured by a one-legged stance
      [Romberg] test and a timed stance test), lymphedema (measured by the circumference of the
      upper arm, wrist, and a finger), body composition (measured by dual energy x-ray
      absorptiometry), and bone mineral density of the heel (measured by ultrasound) are assessed
      at baseline and periodically during the study. Patients also undergo blood and urine sample
      collection for cancer recurrence biomarker and bone remodeling biomarker studies.

      Patients complete questionnaires at baseline and periodically during the study to assess
      demographic (i.e., age, income) and disease-specific (i.e., stage, treatment) variables,
      self-report mental and physical function, presence of chronic medical conditions, symptoms,
      fatigue, exercise outside the study exercise intervention, dietary intake, and psychosocial
      function.
    

Intervention name(s): exercise intervention; laboratory biomarker analysis; questionnaire administration; survey administration; assessment of therapy complications; fatigue assessment and management; management of therapy complications; psychosocial assessment and care
Intervention type(s): Behavioral; Other; Other; Other; Procedure; Procedure; Procedure; Procedure
Intervention description(s): Arm I (progressive, aerobic exercise program): Patients undergo aerobic exercise training over approximately 45 minutes (not including warm-up or cool-down exercises) 3 days a week for 18 months.
Arm II (progressive, resistance exercise program): Patients undergo resistance exercise training 3 days a week for 18 months.; All biomarkers will be measured from urine, blood and plasma obtained from participants by the Oregon Health & Science University (OHSU) General Clinical Research Center (GCRC). Upon exit from the study we will confirm the presence/absence of metastatic disease, via verbal verification by the subject, in order to ensure that biomarkers were primarily reflective of bone turnover changes and not to metastases.; Patients complete questionnaires at baseline and periodically during the study to assess demographic (i.e., age, income) and disease-specific (i.e., stage, treatment) variables, self-report mental and physical function, presence of chronic medical conditions, symptoms, fatigue, exercise outside the study exercise intervention, dietary intake, and psychosocial function.; Administered at measured at baseline, 3, 6, 12, and 18 months; Follow-up every 6 months (measured at baseline, 3, 6, 12, and 18 months ); The Schwartz Cancer Fatigue (SCF) scale, a 6-item scale that specifically assesses the level of subjective fatigue that the participant is currently experiencing. The SCF has been used to measure fatigue in previous exercise studies. The Piper Fatigue Scale (PFS) consists of 22 items and four subscales: behavioral/severity, affective meaning, sensory and cognitive/mood. The scale has been shown to detect reductions in fatigue in cancer patients undergoing behavioral interventions to reduce fatigue, including exercise. Responses are averaged for subscale and total scores with higher scores indicating more fatigue. The PFS has been used to measure fatigue in previous studies of illness and/or medical treatments. 15 minute survey; An interim safety/efficacy review will occur after the first half of enrolled participants completes their 3 month testing appointment (or after 3 months of exercise). The interim safety review will be overseen by OHSU NCI-designated Cancer Institute, while the efficacy review will be conducted by an independent monitor, Dr. George Knafl, a biostatistician in the OHSU School of Nursing, who is not a member of the study personnel.; We will include a 6-item measure of self-efficacy for exercise that has been validated in adults (Nigg, 2002) and has been used by Dr. Bennett (Co-I) in current work in cancer survivors. 5 min. survey
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Supportive Care
Keywords: fatigue; long-term effects secondary to cancer therapy in adults; psychosocial effects of cancer and its treatment; cancer survivor; stage IA breast cancer; stage IB breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; breast cancer in situ