Methods

Study design: single‐centre RCT

Number randomised: 18; 9 to yoga intervention, 9 to wait‐list control

Study start: not reported; stop date: not reported

Length of intervention: 8 weeks

Length of follow‐up: to end of intervention

Country: USA

Participants

Age, years (mean SD):

• Intervention: 63.3 (6.9)

• Control: 62.4 (7.3)

Stage, n (%):

• All women had a diagnosis of stage II‐IV breast cancer.

Inclusion criteria:

• Women with stage II‐IV breast cancer who were at least 2 months post treatment

Exclusion criteria:

• Receiving Herceptin therapy (an immune modifier).

• Pregnant or lactating

• Past or current history of another neoplasm

• Active serious infection, or immune deficiency

• History of psychiatric disorders requiring use of psychoactive medications or of documented alcohol or drug abuse
• Taking current steroid therapy or other known immunomodulating medications

• Physical condition preventing participation in yoga

Interventions

9 participants assigned to exercise intervention:

• Active yoga practice used in this study was primarily physical in nature and included poses traditionally found in beginning Iyengar classes. Sessions were more physically demanding than those of restorative or gentle yoga, with progressing difficulty of poses, including increased duration of weight‐bearing on the arms as individual abilities improved. Two 90‐minute group yoga sessions per week were performed over 8 weeks.

Adherence:

Seven participants in the yoga group who completed the study attended an average of 14 of 16 possible yoga sessions (87.5%) with a range of 12 to 15 sessions.

9 participants assigned to control:

• Control group participants were instructed to continue their regular routines and were offered an opportunity for yoga programme participation at the end of the study period.

Contamination of control group: not reported

Outcomes

Outcomes:

• Quality of life via Functional Assessment of Cancer Therapy Form B (FACT‐B)

• Fatigue by a fatigue score determined by averaging Likert scale responses to fatigue‐related items using the same scoring range

• Salivary cortisol via collected salivary samples using salivette collection vials (Starsedt Inc., Newton, NC) 4 times during the day for 2 consecutive days at baseline and again 8 weeks later. The supernatant was assayed for cortisol via enzyme‐linked immunoassay kits (R&D Systems, Minneapolis, MN).

Numbers of participants assessed:

• Intervention: baseline, 9; at 8 weeks, 7

• Control: baseline, 9; at 8 weeks, 7

Adverse events: not reported

Notes

Trial registration link: none available

Trial authors contacted: no

Intention‐to‐treat analysis: no

Funding: in part by University of Washington Center for Women’s Health and Gender Research, Washington State University Cancer Prevention and Research Center, and in part by Washington State University College of Nursing

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

“Randomly assigned”; method of randomisation was not reported.

Allocation concealment (selection bias)

Unclear risk

Whether allocation was concealed was not reported.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessments was not described.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Analyses included only 14 participants ‐ 7 in each group ‐ who completed the study.

Selective reporting (reporting bias)

High risk

Summary outcomes of FACT‐B were not provided (FACT‐B, FACT‐G, and TOI).

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: single‐centre RCT

Number randomised: 32; 20 to intervention, 12 to control

Study start: not reported; stop date: not reported

Length of intervention: 12 weeks

Length of follow‐up: to end of intervention

Country: USA

Participants

Age, years (mean SD):

• Intervention: 57.4 (6.1)

• Control: 54.9 (6.5)

Stage, n (%):

• Intervention: stage 0, 1 (7.1%); stage I, 5 (35.7%); stage II, 7 (50.0%); stage III, 1 (7.1%); missing, 6

• Control: stage 0, 0 (0.0%); stage I, 5 (41.7%); stage II, 5 (41.7%); stage III, 0 (0.0%); missing, 2

Inclusion criteria:

• Given a diagnosis of stage I‐III cancer, had completed adjuvant treatment within the previous 12 months, and were postmenopausal

• Free of cardiovascular disease and major orthopaedic limitations

• Not regularly active (< 5 days/week)

Interventions

20 participants assigned to exercise intervention:

• 12‐Week home‐based walking programme (3 to 5 days per week of 20 to 30 to 40 minutes at RPE 10 to 11 to 12 to 15 by week 8) using the Active Choices model developed and refined by King and colleagues. Primary purpose of the intervention was to increase walking. Participants received a brief (˜30 minutes) in‐person counselling session, followed by 5 short (10 to 15 minutes each) telephone counselling calls during weeks 1, 2, 4, 7, and 10.

• Initial one‐on‐one counselling session focussed on goal setting and exercise safety. Subsequent counselling calls applied key constructs of the social cognitive theory, whereby the counsellor and participants discussed a specific behaviour change principle (e.g. social support, rewards) that participants could use to increase their walking.

Adherence:

• On average, participants completed 86.2 ± 11.9% (range 62.1% to 100%) of prescribed walking sessions each week (missing logs were assigned zeros for the number of walking sessions completed during those particular weeks; data not shown).

12 participants assigned to control:

• Usual care control group asked to maintain usual physical activity levels throughout the 12‐week study period. Study staff had contact with this group only at follow‐up appointments. Upon completion of the study, women in the usual care control group received baseline intervention counselling session, materials, and pedometer.

Contamination of control group: not reported

Outcomes

Outcomes:

• QoL assessed via 2 measures:

  • Medical Outcomes 36‐Item Short Form Health Survey (MOS SF‐36)

  • International Breast Cancer Study Group (IBCSG) QoL Core Questionnaire, breast cancer‐specific questionnaire, developed to measure the impact of adjuvant therapy on QoL. Questionnaire consists of 10 single‐item visual analogue scales, anchored at both ends with words describing highest and lowest extremes of item content.

• 13‐Item subscale of the Functional Assessment of Cancer Therapy: Fatigue (FACT‐Fatigue) questionnaire used to assess fatigue

• Completed 41‐item validated Community Health Activities Model Program for Seniors (CHAMPS) questionnaire

Numbers of participants assessed:

• Intervention: baseline, 20; at 12 weeks, 18

• Control: baseline, 12; at 12 weeks, 12

Adverse events: none reported

Notes

Trial registration link: none available

Trial authors contacted: yes, for additional data (means and SDs for outcomes), but trial authors did not reply

Intention‐to‐treat analysis: no

Funding: supported by the US Army, Grant # DAMD17‐01‐1‐0628

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"Participants were randomized 2:1 (intervention: control)".

It is unclear how the allocation sequence was generated.

Allocation concealment (selection bias)

Unclear risk

Whether treatment assignment was concealed from study personnel and participants was not described.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessments was not described.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Post‐test data at 12 weeks were collected on 94% of participants; only completers were analysed.

Selective reporting (reporting bias)

High risk

Physical activity data post intervention were not reported.

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: single‐centre RCT

Number randomised: 60; 30 to intervention, 25 to standard care

Study start: April 2003; stop date: April 2004

Length of intervention: 6 months

Length of follow‐up: to end of intervention

Country: USA

Participants

Age, years (mean SD):

• Intervention: 55.7 (11.1)

• Control: 54.4 (11.7)

Stage, n (%):

• Intervention: DCIS, 9 (27); stage I, 9 (27); stage II, 7 (21); stage III, 8 (24); stage IV, 1 (3); missing, 1

• Control: DCIS, 4 (17); stage I, 8 (33); stage II, 8 (33); stage III, 3 (13); stage IV, 1 (4); missing, 1

Inclusion criteria:

• Within 7 years of a breast cancer diagnosis

• No longer receiving treatment for breast cancer (except hormone therapy)

• Not engaging in focussed moderate physical activity for 30 minutes or longer a day most days of the week

Exclusion criteria:

• Clearance received from physician to ensure that they had no medical conditions contraindicating moderately intensive exercise

Interventions

35 participants assigned to exercise intervention:

• Participants in the lifestyle programme attended 90‐minute group meetings each week for 16 weeks, and every other week for 8 weeks (21 sessions total). Behaviour change methods were based on the transtheoretical model. Participants were taught to assess their motivational readiness for physical activity, which they did every 4 to 5 weeks, and received booklets about increasing physical activity matched to their stage of readiness.

• Intervention sessions emphasised information and skills such as benefits of physical activity, making small changes, overcoming barriers, goal setting, rewarding yourself, and self‐monitoring. Several methods of self‐monitoring were used, including recording minutes of activity and recording steps using a pedometer. Information and skills were sequenced so that cognitive methods (e.g. recognising benefits of physical activity) were presented in earlier sessions and behavioural methods (e.g. monitoring steps, rewarding yourself) were presented in later sessions.

Adherence:

Among those who started the intervention, the mean number of sessions attended was 14.6 out of 21 (SD 5.1), with a range of 2 to 21 sessions.

25 participants assigned to control:

• During 6‐month intervention period, standard care participants received 2 mailings of the same written material as the intervention group, which included topics related to breast cancer survivorship but did not address physical activity, and standard care participants did not meet as a group.

Outcomes

Outcomes:

• Physical activity during the past week assessed via a 7‐day physical activity recall questionnaire (7‐ DPAR), an interviewer‐administered measure

• Physical performance assessed via a 6‐minute endurance walk test; a 50‐foot walk test; a timed sit‐to‐stand test; a timed reach‐up test; and a forward‐reach test

• Anthropometric measures such as BMI, hip and waist circumferences

• Quality of life assessed via Medical Outcomes 36‐Item Short Form Health Survey

• Patient satisfaction measured via a brief questionnaire administered to participants in the lifestyle programme during the last session of the programme

• Lymphoedema assessed by a physical therapist who measured arm girth circumferentially at predetermined bilateral points. Jobst measuring tapes were used to take circumferential measurements every inch and a half, starting at the elbow and moving toward the shoulder and toward the wrist.

Numbers of participants assessed:

• Intervention: baseline, 35; at 6 months, 28

• Control: baseline, 25; at 6 months, 23

Adverse events: The intervention group did not show a significantly larger number of increases in arm circumference compared with the standard care group.

Notes

Trial registration link: none available

Trial authors contacted: no

Intention‐to‐treat analysis: yes

Funding: grants R21 CA89519 and R25 CA57730 from the National Cancer Institute

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

“Participants were assigned to study arms using a form of adaptive randomization called minimization”.

Allocation concealment (selection bias)

Unclear risk

Whether the allocation was concealed is unclear.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Staff conducting assessments were blind to participants’ study condition.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All participants who were randomised were included in the analysis, regardless of their attendance at intervention sessions. Data for participants who did not complete the 6‐month assessment were imputed based on regression models predicting outcomes in the remaining sample, using covariates and design variables.

Selective reporting (reporting bias)

Unclear risk

No selective reporting of outcomes is apparent.

Other bias

High risk

Imbalance between numbers allocated to intervention and control groups could potentially lead to additional bias.

Methods

Study design: single‐centre RCT

Number randomised: 18; 9 to intervention, 9 to control

Study start, not reported; stop date, not reported

Length of intervention: 8 weeks

Length of follow‐up: to end of intervention

Country: USA

Participants

Age:

• Ages 48 to 69 years

Stage:

• Stage I‐III breast cancer

Inclusion criteria:

• Minimum of 8 weeks post chemotherapy

• Oestrogen receptor positive status

• Surgery for lumpectomy, modified mastectomy, or full mastectomy (with/without reconstruction)

• Life expectancy greater than 6 months

• Adequate blood cell counts and kidney, liver, and cardiac function

• Physical and mental ability to attend all yoga training sessions

Exclusion criteria:

• Receiving Herceptin therapy, current steroid therapy, or other known immunomodulating medications

• Pregnancy or current lactation

• Past or current history of another neoplasm, active serious infection, or immune deficiency
• Documented alcohol or drug abuse

• History of psychiatric disorders requiring use of psychotropic medications

Interventions

9 participants assigned to exercise intervention:

• Beginning level Iyengar yoga class 3 times per week (2 supervised and 1 home‐based). Attention to alignment and symmetry, use of props, and careful sequencing all improve stamina, strength, flexibility, and confidence, while decreasing stress and side effects.

Adherence: not reported

9 participants assigned to control:

• Wait‐list control

Outcomes

Outcomes:

• 31‐Question self‐report survey about reasons for participation, feelings of stress, level of physical and mental effort during class sessions, and perceptions about how yoga practice influenced awareness

Numbers of participants assessed:

• Intervention: at 6 weeks, 9

• Control: at 6 weeks, 9

Adverse events: not reported

Notes

Trial registration link: none available

Trial authors contacted: no

Intention‐to‐treat analysis: unclear

Funding: not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"Women were randomized", but it was unclear how the allocation sequence was generated.

Allocation concealment (selection bias)

Unclear risk

Whether treatment assignment was concealed from study personnel and participants was not described.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessments was not described.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

It is unclear how many participants were included in each outcome assessment.

Selective reporting (reporting bias)

High risk

Outcome measures were poorly described and reported. Scores for each question were not reported.

Other bias

High risk

Outcomes were not assessed at baseline, so it was not possible to assess whether outcomes changed as a result of intervention.

Methods

Study design: single‐centre RCT
Number randomised: 31; 16 to intervention, 15 to control
Study start: March 2007; stop date: July 2010
Length of intervention: 12 weeks
Length of follow‐up: to end of intervention, at 3 months post intervention

Country: USA

Participants

Age, years (mean SD):

• Intervention: 54.4 (5.7)

• Control: 53.3 (4.9)

Stage, n (%):

• Stage 0‐II

Inclusion criteria:

• Original diagnosis of stage 0‐II breast cancer

• Completed local and/or adjuvant cancer therapy (with the exception of hormone therapy) at least 6 months previously

• Ages 40 to 65 years

• Postmenopausal

• No other cancer in the past 5 years

• Experiencing persistent cancer‐related fatigue

Exclusion criteria:

• Chronic medical conditions or regular use of medications associated with fatigue (e.g. untreated hypothyroidism, diabetes, autoimmune disease, anaemia (defined as haematocrit < 24), chronic fatigue syndrome)

• Evidence that fatigue was driven primarily by a medical or psychiatric disorder other than cancer (e.g. current major depression, insomnia, sleep apnoea)

• Evidence that fatigue was driven primarily by other non‐cancer‐related factors (e.g. shift work, recent change in activity or schedule)
• Physical problems or conditions that could make yoga unsafe (e.g. serious neck injury, unstable joints)

• Body mass index (BMI) > 31 kg/m²

Interventions

16 participants assigned to exercise intervention:
• Iyengar yoga, a traditional form of Hatha yoga, performed in groups of 4 to 6 women for 90 minutes twice a week for 12 weeks

Adherence:

Over 80% of participants attending at least 20 of the 24 yoga classes offered. Mean number of classes attended was 18.9 of 24 classes (78%), and median number was 22 of 24 classes (92%). At 3‐month follow‐up, 9 of 14 women who attended the yoga classes (64%) were continuing to use techniques learned in class.

Control group: 15 assigned to control:
• Health education classes conducted for 120 minutes once a week for 12 weeks (24 hours) in groups of 4 to 7 women. Classes were led by a PhD‐level psychologist with clinical experience.

Adherence:

In the education group, the mean number of classes attended was 9.2 of 12 classes (77%), and the median number was 11 of 12 classes (92%).

Outcomes

Primary outcome:

• Subjective fatigue severity assessed with the Fatigue Symptom Inventory (FSI)

Secondary outcomes:

• Vigour assessed by the vigour subscale of the Multi‐dimensional Fatigue Symptom Inventory (MFSI)

• Depressive symptoms assessed via the Beck Depression Inventory‐II (BDI‐II)

• Subjective sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI)

• Feelings of stress assessed on the Perceived Stress Scale

• Timed chair‐stands used to assess lower extremity strength and endurance

• Functional reach test used to assess strength, flexibility, and balance

• Self‐efficacy for managing fatigue assessed via the fatigue subscale of the Human Immunodeficiency Virus Self‐Efficacy Questionnaire adapted for breast cancer

• Fatigue interference with activities, mood, and enjoyment of life assessed with the interference subscale of the FSI

Numbers of participants assessed:

• Intervention: n = 16 at baseline, n = 14 post intervention, n = 13 months after intervention

• Control: n = 15 at baseline, n = 13 post intervention, n = 13 months after intervention

.Adverse events: none reported

Notes

Trial registration link: none available

Trial authors contacted: no

Intention‐to‐treat analysis: yes

Funding: National Center for Complementary and Alternative Medicine/National Institutes of Health (NCCAM/NIH U01‐AT003682; Iyengar Yoga for Breast Cancer Survivors with Persistent Fatigue)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"Allocation sequence was generated independently by the study statistician", but it is unclear how the allocation sequence was generated.

Allocation concealment (selection bias)

Unclear risk

"Allocation was concealed in opaque envelopes" but whether "sequential" is not mentioned.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to blind participants; however, it is unclear whether the outcome was influenced by lack of masking.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

"Outcomes assessors for the performance tasks were blinded to group assignment, and all were trained in standardized testing procedures".

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"All statistical analyses were performed on an intent‐to‐treat basis". Mixed model analysis was used to account for missing data.

Selective reporting (reporting bias)

Low risk

No selective reporting of outcomes is apparent.

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: single‐centre RCT

Number randomised for 6‐month study: 75; to intervention; 37, to control, 38

Number randomised for 12‐month study: 50; to intervention, 25; to control, 25

Study start: March 2004; stop date: July 2006

Length of intervention: 6 months; subsample study: 12 months

Length of follow‐up: to end of intervention

Country: USA

Participants

Age, years (mean SD):

• Intervention: 56.5 (9.5)

• Control: 55.1 (7.7)

Stage, n (%):

• Intervention: in situ, 4 (11); stage I, 20 (54); stage II, 10 (27), stage IIIA, 3 (8)

• Control: in situ, 4 (11); stage I, 10 (27); stage II, 18 (46), stage IIIA, 6 (16)

Inclusion criteria:

• Postmenopausal women

• Ages 40 to 75 years

• Stage 0‐IIIA breast cancer

• 1 to 10 years post diagnosis

• ≥ 12 months post completion of adjuvant treatment

• Physically able to exercise and physician consent to begin an exercise programme

• Sedentary activity pattern (< 60 minutes/week)

Exclusion criteria:

• Diagnosis of recurrent or other primary cancer event

• Current smoker

• Diabetes mellitus

• Current or planned enrolment in a structured weight loss programme

Interventions

37 participants assigned to exercise intervention:

• Exercise intervention consisted of a combined supervised training programme at a local health club and a home aerobic training programme. Participants exercised at the health club during designated sessions 3 times per week and were instructed to exercise 2 days/week on their own, either at the health club or at home.

• Intervention consisted primarily of walking, although participants could choose to meet the exercise goal through other forms of aerobic activity. Participants were asked to perform three 15‐minute sessions during week 1, building to five 30‐minute moderate‐intensity sessions by week 5. Exercise started at 50% of predicted maximal heart rate (220‐age) and was gradually increased to approximately 60% to 80% of predicted maximal heart rate.

Adherence:

• Exercise group participants averaged 123 minutes/week (SD 52) of moderate‐to‐vigorous‐intensity sports/recreational activity (range 0 to 637)

• 34% of exercisers met the study goal of 150 minutes/week

• 56% completed at least 120 minutes/week (80% of the study goal)

• 67% attended supervised exercise sessions

• 96% reported exercising at least twice per week at home

38 participants assigned to control:

• Control groups were told that they could exercise on their own if they chose, but that the study’s physical activity programme would not be available to them. They received all exercise programme materials at 6‐month follow‐up. Participants in both groups were also asked not to make significant changes in their dietary habits.

Outcomes

Outcomes:

• Happiness assessed by the 2‐item Fordyce Happiness Measure

• Self‐esteem assessed on the Rosenberg Self‐Esteem (RSE) Scale

• Depression assessed via the Centers for Epidemiological Studies—Depression Scale (CES‐D)

• Anxiety assessed by the State‐Trait Anxiety Index (STAI)

• Stress assessed on Cohen’s 10‐Item Perceived Stress Scale

• Quality of life (QoL) assessed by FACT‐B and Medical Outcomes 36‐Item Short Form Health Survey (MOS SF‐36)

• Physical activity assessed via a 7‐day physical activity log (PAL) and daily steps recorded on a 7‐day pedometer log

• Anthropometric measurements including body weight, body mass index (BMI), total percent body fat, and lean mass obtained with whole‐body dual‐energy X‐ray absorptiometry (DEXA)

• Bone mineral density and bone mineral content via DEXA

• Waist and hip circumferences

• Insulin and plasma concentrations of total insulin‐like growth factor‐1 (IGF‐1) and insulin‐like growth factor binding protein‐3 (IGFBP‐3) measured in serum with an enzyme‐linked immunosorbent assay (ELISA) kit

• Systolic and diastolic blood pressure (available for 65 participants)

• Metabolic variable assays, fasting high‐density lipoprotein (HDL‐C), triglycerides, blood glucose (all enzymatically measured via Alfa Wassermann ACE Alera Chemistry Analyzer with reagents supplied by the company), and metabolic syndrome z‐score (all outcomes available for 65 participants)

Numbers of participants assessed:

• Intervention: baseline, 37 (35 for metabolic variable assays); at 6 months, 37 (35 for metabolic variable assays)

• Control: baseline, 38 (30 for metabolic variable assays); at 6 months, 37 (30 for metabolic variable assays)

Adverse events: none reported

Notes

Trial registration link: none available

Trial authors contacted: no

Intention‐to‐treat analysis: yes but last observation carried forward (LOCF)

Funding: Lance Armstrong Foundation, American Cancer Society, Susan G. Komen. In part by the National Center of Research Resources (NIH)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random number generator was used.

Allocation concealment (selection bias)

Low risk

“The randomization code for each participant was obtained by the principal investigator (who was not involved in recruitment or data collection) only after baseline measures for that individual had been completed and staff conducting clinic visits did not have access to the randomization program”.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Study personnel and outcome assessors were not masked or blinded to study interventions.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Last observation carried forward (LOCF) approach was used; “baseline QoL values were carried forward”.

Selective reporting (reporting bias)

Low risk

No selective reporting of outcomes is apparent.

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: single‐centre RCT

Numbers allocated, 68; 34 to exercise intervention; 34 to usual care

Study start: March 2009; stop date: June 2010

Length of intervention: 8 weeks

Length of follow‐up: at 6 months after discharge

Country: Spain

Participants

Age, years (mean SD):

• Intervention: 48.4 (10.8)

• Control: 46.2 (7.4)

Stage, n (%):

• Intervention: stage I, 4 (12.4); stage II, 23 (72.0); stage IIIA, 5 (15.5)

• Control: stage I, 10 (34.4); stage II, 14 (48.3); stage IIIA, 5 (17.3)

Inclusion criteria:

• Between 25 and 65 years old with a diagnosis of breast cancer (stage I‐IIIA)

• Finished oncology treatment except hormone therapy in the previous 18 months

• Exhibit clinically significant fatigue (> 3 in total score on the Piper Fatigue Scale)

Exclusion criteria:

• Receiving oncology treatment at the time of the study

• Physical limitations associated with orthopaedic conditions

Interventions

34 participants assigned to exercise intervention:

• 8‐Week water‐based intervention was carried out 3 times per week for a duration of 60 minutes (10 minutes of warm‐up, 40 minutes of aerobic and endurance exercises, and 10 minutes of cool‐down exercises) in an indoor heated swimming pool sized 25 × 12.5 m, with 140 to 200 cm water depth, 28°C of water temperature, and 30°C of room temperature.

• Aerobic exercises consisted of different horizontal movements: forward and backward jogging with arms moving, pulling, and pressing; leaps, leg cross‐overs, and hopping movements focussing on movement in multiple directions. Endurance exercises were considered moderate as the parameters set for each exercise included 2 to 3 sets of 8 to 12 repetitions.

Adherence:

• 34 participants finished the aquatic exercise programme and completed 84% of the 24 physical therapy sessions (mean ± SD, 20 ± 4 sessions).

34 participants assigned to control:

• Participants allocated to the usual care group followed oncologist recommendations for maintaining a healthy lifestyle based on adequate nutrition, energy balance, and maintaining usual activities.

Outcomes

Primary outcomes:

• Piper Fatigue Scale (PFS) score

Secondary outcomes:

• Mood state assessed via the Spanish version of the Profile of Mood States (POMS) containing 63 adjectives rated by participants on a 5‐point scale

• Lower body muscular strength assessed via the “multiple sit‐to‐stand test” involves counting the time in seconds needed by participants to rise until they reach full knee extension and sit back, 10 times, as fast as possible

• Muscular endurance of abdominal muscles tested via the trunk curl static endurance test

Numbers of participants assessed:

• Intervention: baseline, 34; at 8 weeks, 34; at 6 months, 32

• Control: baseline, 34; at 8 weeks, not stated; at 6 months, 29

Adverse events: Adverse effects reported during the study included discomfort or low‐intensity pain/stiffness after an exercise session in 3 participants; nevertheless, they continued the programme.

Notes

Trial registration link: none available

Trial authors contacted: no

Intention‐to‐treat analysis: no

Funding: Health Institute Carlos III and PN I+D+I 2008‐2011, Madrid, Spanish government (grant no. FIS PI10/02749); Research Office of the University of Granada, Spain

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated numbers produced a sequence that was entered into opaque envelopes.

Allocation concealment (selection bias)

Low risk

“Computer‐generated number sequence was entered into opaque envelopes. These envelopes were opened by a blinded researcher after the first outcome measurement”.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Assessors were blinded to treatment allocation.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Only those who completed postintervention and 6‐month assessments were included in analysis.

Selective reporting (reporting bias)

Low risk

No selective reporting of outcomes is apparent.

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: single‐centre RCT

Number randomised: 37; 17 to intervention, 20 to control

Study start: June 2005; stop date: October 2006

Length of intervention: 8 weeks

Length of follow‐up: at 8 weeks, at 3 months

Country: USA

Participants

Age, years (mean SD):

• Intervention: 53.9 (9.0)

• Control: 54.9 (6.2)

Stage, n (%):

• Intervention: stage IA, 7 (41.2); stage IIA, 5 (29.4); stage IIB, 5 (29.4)

• Control: stage IA, 8 (40.0); stage IIA, 6 (30.0); stage IIB, 6 (30.0)

Inclusion criteria:

• At least 1 hot flash per day on 4 or more days per week

• No signs of active breast cancer

• No current cytotoxic chemotherapy

• Diagnosis of breast cancer at stage IA‐IIB ≥ 2 years before

• No hormone replacement therapy currently or within prior 3 months

• Stabilised on a constant regimen of menopausal symptom medications and supplements for at least 3 weeks

• Taking antidepressants, stabilised at a fixed dose for at least 3 months

Exclusion criteria:

• Resided > 70 miles from the research site and thus were less likely to attend intervention sessions

• Unavailable to attend the intervention on the day and at the time offered (most yoga groups were scheduled so as to be accessible to women holding full‐time day jobs)

• Currently engaged in intensive yoga practice (> 3 days/week)

• Received treatment for serious psychiatric disorders (e.g. schizophrenia) in the previous 6 months

• Not English speaking

Interventions

17 participants assigned to exercise intervention:

• Yoga of Awareness including yoga postures, breathing techniques, meditation, study of pertinent topics, group discussion. Once per week (participants were encouraged to spend time practicing yoga strategies daily at home, but actual adherence to this was not reported) for a duration of 40 minutes over 8 weeks

Adherence:

On average, participants attended 6 of the 8 classes (range 0 to 8). Only 3 women attended < 4 classes. Adherence to daily yoga practice, average 30 minutes/d at post and 16 minutes at 3 months

Control group: 20 assigned to control:

• Wait‐list

Outcomes

Treatment outcomes. assessed via a brief daily diary measurement strategy

• Daily menopausal symptoms on 0 to 9 scales in which higher scores reflected greater amounts, common menopausal symptoms across the preceding 24 hours: hot flash frequency, hot flash severity, joint pain, fatigue, negative mood, sleep disturbance, night sweats, and bother (menopausal symptom‐related distress). Primary outcome of hot flash total scores was computed as frequency × severity.

• With 0 to 9 scales in which higher scores reflected greater amounts, 3 therapeutic processes targeted by the Yoga of Awareness programme—relaxation, vigour, and acceptance—were assessed by telephone voice system diaries.

• Minutes spent in daily yoga practice (post and follow‐up assessments only)

Numbers of participants assessed:

• Intervention: n = 17 at baseline, n = 13 at 8 weeks, n = 13 at 3 months

• Control: n = 20 at baseline, n = 17 at 8 weeks, n = 17 at 3 months

Adverse events: not reported

Notes

Trial registration link: none available

Trial authors contacted: yes, for means and SDs for outcomes. However, trial authors did not provide these data.

Intention‐to‐treat analysis: no

Funding: Susan G. Komen Breast Cancer Foundation

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random number table was used.

Allocation concealment (selection bias)

High risk

"Concealed in envelopes"; sequential sequencing or opaque envelopes were not mentioned.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to blind participants; however, it is unclear whether the outcome was influenced by lack of masking.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Research assistant collecting assessment data was kept blind with regard to participant condition assignments.

Incomplete outcome data (attrition bias)
All outcomes

High risk

No ITT, and no mention of how missing data were handled. 8 participants did not complete the intervention.

Selective reporting (reporting bias)

Low risk

No selective reporting of outcomes is apparent.

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: single‐centre RCT
Number randomised: 20; 10 to exercise, 10 to control
Study start and stop dates: not reported
Length of intervention: 16 weeks
Length of follow‐up: to end of intervention

Country: Italy

Participants

Age, years (mean SD):

• Intervention: 45.3 (4.3)

• Control: 46.0 (2.8)

Stage, n (%):

• Intervention: stage I, 3 (30); stage II, 5 (50); stage III, 2 (20)

• Control: stage I, 1 (10); stage II, 5 (50); stage III, 4 (40)

Inclusion criteria:

• Age 40 to 50 years

• Conclusion of all cancer‐related treatments at least 6 months previously

• Mastectomy

• No external physical activity for at least the preceding 12 months

• Medical eligibility for non‐competitive athletic activity

Interventions

10 participants assigned to exercise intervention:

• All intervention group participants received two 1‐hour therapeutic horse‐riding treatments at an intensity of 65% to 70% of HR maximum (220‐age) per week, for 16 weeks. Each riding session consisted of 3 phases: (1) warm‐up, horse‐caring, and grooming; (2) riding; and (3) unsaddling and grooming activities.

Adherence: not reported

10 assigned to control:

• Participants randomly assigned to control group were instructed not to begin any new formal physical exercise programme

Outcomes

Outcomes:

• Maximal oxygen consumption (VO₂max) obtained via the Astrand–Rhyming cycle ergometer test

• Maximal strength of principal muscle groups assessed by an inertial measurement system (Free‐Power; Sensorize, Rome, Italy). Maximal strength evaluated for each of 5 weight lifting machines (Technogym SpA, Cesena, Italy): leg press, leg extension, leg curl, shoulder press, and vertical traction. Participants were asked to perform at least 2 repetitions at 30%, 50%, and 70% of presumed 1RM.

• Body composition (fat mass % and total body water %) assessed via a portable multi‐frequency digital bioelectrical impedance device (Handy 3000; DS Medica, Milano, Italy)

• Quality of life assessed via FACT‐G

• Fatigue assessed by FACT‐F

Numbers of participants assessed:

• Intervention: baseline, 10; at 16 weeks, 10

• Control: baseline, 10; at 16 weeks, 10

Adverse events: none reported

Notes

Trial registration link: none available

Trial authors contacted: no

Intention‐to‐treat analysis: no dropouts reported

Funding: not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"Patients were randomly divided into two groups". It is unclear how the allocation sequence was generated.

Allocation concealment (selection bias)

Unclear risk

Whether treatment assignment was concealed from study personnel and participants was not described.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to blind participants.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Whether study personnel and outcome assessors were masked or blinded to study interventions was not reported.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No dropouts were reported.

Selective reporting (reporting bias)

Low risk

No selective reporting of outcomes is apparent.

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: RCT

Number randomised: 62; 22 to high‐load resistance exercise, 21 to low‐load resistance exercise, 19 to control

Study start: June 2010; stop date: not stated

Length of intervention: 3 months

Length of follow‐up: to end of intervention

Country: Australia

Participants

Age, years (mean SD):

• High‐load resistance exercise (HLRE): 56.1 (8.1)

• Low‐load resistance exercise (LLRE): 57.0 (10.0)

• Control: 58.6 (6.7)

Stage, n (%):

• HLRE: stage I, 2 (9.1); stage II, 18 (81.8); stage III, 2 (9.1)

• LLRE: stage I, 5 (23.8); stage II, 10 (47.6); stage III, 6 (28.6)

• Control: stage I, 6 (31.6); stage II, 9 (47.3); stage III, 4 (21.1)

Time since cancer diagnosis, mean (SD) years:

• HLRE: 5.9 (6.1)

• LLRE: 6.1 (5.2)

• Control: 9.5 (9.8)

Inclusion criteria:

• Histological diagnosis of breast cancer at least 1 year before the study

• Clinical diagnosis of breast cancer‐related lymphoedema and medical clearance from general practitioner

• Clinical diagnosis of lymphoedema defined as having at least a 5% inter‐limb discrepancy in volume or circumference at the point of greatest visible difference

Exclusion criteria:

• Unstable lymphoedema defined as receiving intensive therapy (i.e. decongestive therapy or antibiotics for infection) within the previous 3 months

• Musculoskeletal, cardiovascular, and/or neurological disorder that could inhibit exercise

Interventions

43 participants assigned to 1 of 2 resistance exercise interventions

• Two 60‐minute exercise sessions were performed per week for 3 months. Intensity varied across conditions (moderate‐high (12 to 16 RPE); high‐load, 75% to 85% of 1RM using 10‐6 RM, 1 to 4 sets per exercise; low‐load, 55% to 65% of 1RM using 20‐15 RM, 1 to 4 sets per exercise)

• Exercise sessions were conducted in groups of up to 8 to 10 participants. The resistance exercise regimen included 6 exercises that targeted major upper body muscle groups including chest, back, shoulders, upper arms, and forearms (chest press, seated row/lat pulldown, shoulder press/lateral raise, biceps curl, triceps extension, and wrist curl). Additionally, 2 exercises targeting major muscle groups of the lower body were performed (leg press/leg extension, squat/lunge).

Adherence:

Exercise attendance was high for both resistance training groups, with an average of 23.2 ± 1.9 out of a possible 24 sessions attended (HLRE 23.4 ± 1.1; LLRE 22.9 ± 2.4).

19 participants assigned to control:

• Participants randomised to the control group were offered the exercise programme after completion of the intervention period. All participants were instructed to maintain their usual lymphoedema self‐care management regimen, physical activity levels, and diet throughout the intervention period.

Outcomes

Primary outcome:

• Severity of swelling associated with breast cancer‐related lymphoedema assessed via standard objective measures:

  • Bioimpedance spectroscopy (BIS) impedance ratio

  • DEXA

  • Arm circumference measurements

Secondary outcomes:

• Severity of symptoms assessed via:

  • Disability of the Arm, Shoulder, and Hand questionnaire (DASH)

  • Brief pain inventory questionnaire (BPI)

  • Arm morbidity subscale of the Functional Assessment of Chronic Illness Therapy breast cancer questionnaire for patients with lymphoedema (FACT‐B+4)

  • Arm symptoms subscale of the European Organization for Research and Treatment of Cancer breast cancer module (QLQ‐BR23)

• Maximal grip strength tested with an isometric hand dynamometer (Model 78011; Lafayette Instruments, Lafayette, IN, USA). Affected and non‐affected limbs were assessed individually, and the best of 3 trials was reported.

• Maximal strength of major muscle groups assessed by the 1RM method in chest press, seated row, and leg press exercises

• Muscle endurance assessed by a repetition maximum test, which involved participants performing the maximal number of repetitions possible with 70% of current 1RM in the chest press, seated row, and leg press

• Range of motion about the wrist, elbow, and shoulder assessed by standard goniometric techniques

• Health‐related QoL assessed with MOS SF‐36

Numbers of participants assessed:

• HLRE: baseline, 22; at 3 months, 22

• LLRE: baseline, 21; at 3 months, 21

• Control: baseline, 19; at 3 months, 19

Adverse events: No lymphoedema exacerbations or any other adverse events were reported.

Notes

Trial registration link: ACTRN12610000788077 (http://www.anzctr.org.au/ACTRN12610000788077.aspx)

Trial authors contacted: no

Intention‐to‐treat analysis: yes, but using LOCF

Funding: Edith Cowan University and University of Canberra

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Participants were randomised in an allocation ratio of 1:1:1 by a random assignment computer programme.

Allocation concealment (selection bias)

Low risk

Exercise physiologists involved in assigning participants to groups were blinded to the allocation sequence.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding of outcome assessments was not described.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Missing data were addressed by imputing change across time as zero.

Selective reporting (reporting bias)

Low risk

No selective reporting of outcomes is apparent.

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: single‐centre RCT

Number randomised: 53; intervention, 25; control, 28

Study start: May 2001; stop date: June 2001

Length of intervention: 15 weeks

Length of follow‐up: to end of intervention

Country: Canada

Participants

Age, years (mean SD):

• Intervention: 59 (5)

• Control: 58 (6)

Stage, n (%):

• Intervention: stage I, 10 (42); stage IIA, 6 (25); stage IIB, 6 (25); stage IIIA, 2 (8)

• Control: stage I, 11 (39); stage II A, 11 (39); stage IIB, 5 (18); stage IIIA, 1 (4)

Inclusion criteria:

• Histologically confirmed stage I‐IIIB breast cancer

• Diagnosis between January 1999 and June 2000

• Completed surgery, radiotherapy, and/or chemotherapy (≥ 6 months before randomisation) with or without current tamoxifen or arimidex therapy

• Postmenopausal (not experiencing menstrual periods for previous 12 months)

• Non‐smokers (not smoking for previous 12 months)

• Between 50 and 69 years of age

• English‐speaking

• Willing to travel to the exercise facility

Exclusion criteria:

• Known cardiac disease

• Uncontrolled hypertension

• Uncontrolled thyroid disease

• Diabetes

• Mental illness

• Infection

• Immune or endocrine abnormality

• Body weight reduction ≥ 10% in the past 6 months

• Positive exercise stress test

Interventions

25 participants assigned to exercise intervention:

• Participants trained 3 times per week for 15 weeks on recumbent or upright cycle ergometers. Exercise intensity was set at the power output that elicited the ventilatory equivalent for carbon dioxide to ensure optimal training adaptations. This training intensity corresponds to approximately 70% to 75% of VO₂max in untrained participants. Exercise duration began at 15 minutes for weeks 1 through 3, then systematically increased by 5 minutes every 3 weeks thereafter to 35 minutes for weeks 13 through 15.

Adherence:

Exercise group completed 98.4% (44.3 of 45) of prescribed exercise sessions.

28 participants assigned to control:

• Control group did not train and were asked not to begin a structured exercise programme. To reduce attrition, control group was offered the intervention after the trial ended.

Outcomes

Primary outcomes:

• VO₂peak

• Overall QoL assessed by FACT‐B scale and FACT‐General (FACT‐G) scale

• Natural killer (NK) cell cytotoxic activity in isolated peripheral blood mononuclear cells

• C‐reactive protein (CRP) assessed in serum by enzyme‐linked immunosorbent assay kit

Other outcomes:

• Peak power output, oxygen consumption, and power output at the ventilatory equivalent for oxygen, and oxygen consumption and power output at the ventilatory equivalent for carbon dioxide

• QoL outcomes such as happiness assessed by the Happiness Measure, self‐esteem assessed on the RSE scale, and fatigue assessed via FACT‐F

• Body composition outcomes were body weight, BMI, and sum of skinfolds (biceps, triceps, subscapular, suprailiac, and medial calf)

• Exercise outside of the exercise intervention monitored via the Leisure Score Index (LSI) of the Godin Leisure‐Time Exercise Questionnaire

• Fasting insulin, glucose, insulin resistance, IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐3, and IGF‐I:IGFBP‐3 molar ratio

• Whole blood neutrophil function, phenotypes of isolated mononuclear cells, estimations of unstimulated and phytohemagglutinin (PHA)‐stimulated mononuclear cell function {rate of [3H] thymidine uptake, production of proinflammatory [interleukin (IL)‐1alpha, tumour necrosis factor, TNF‐alpha, IL‐6] and anti‐inflammatory cytokines (IL‐4, IL‐10, transforming growth factor‐beta 1)}

• Blood pressure measurements obtained by trained, certified individuals who used a random zero sphygmomanometer

• Total cholesterol, high‐density lipoprotein cholesterol (HDL‐C), triglycerides (TGs), and low‐density lipoprotein cholesterol (LDL‐C) calculated via the Friedewald formula. TC:HDL‐C ratio calculated as total cholesterol divided by HDL‐C

Numbers of participants assessed:

• Intervention: baseline, 25; at 15 weeks, 24

• Control: baseline, 28; at 15 weeks, 26

Adverse events:

• Intervention: lymphoedema (n = 3), gynaecological complication (n = 1), influenza (n = 1)

• Control: foot fracture (n = 1), bronchitis (n = 1)

Notes

Trial registration link: none available

Trial authors contacted: no

Intention‐to‐treat analysis: no

Funding: NCIC, CCS, Canadian Institutes of Health Research, Izaak Walton Killiam Memorial Scholarship, Alberta Heritage Foundation for Medical Research studentship

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random numbers table. Block permutation procedure was used.

Allocation concealment (selection bias)

Low risk

“The allocation sequence and group assignments were generated by a research assistant and then enclosed in sequentially numbered and sealed envelopes”.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Participants were not blinded for self‐report measures. Participants were blinded to their exercise test results until after the trial. Exercise physiologists were blinded for physical outcome measures. Laboratory staff and those who assessed study endpoints were blinded to treatment assignment.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

One study participant withdrew from the intervention group. Two participants withdrew from the control group and were not included in cardiopulmonary outcome analyses. Only 1 participant who had withdrawn from the exercise group was missing from QoL analyses.

Selective reporting (reporting bias)

Low risk

No selective reporting of outcomes is apparent.

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: single‐centre quasi‐RCT

Number randomised: 42; 22 to intervention, 20 to control

Study start: September 2010; stop date: July 2012

Length of intervention: 8 weeks

Length of follow‐up: to end of intervention

Country: Spain

Participants

Age, years (mean SD):

• Intervention: 47.3 (6.6)

• Control: 48.7 (9.7)

Stage, n (%):

• Not reported

Inclusion criteria:

• History of primary breast cancer

• Within 1 year of cancer diagnosis

• Aged 25 to 65 years

• Post cancer treatment in the past 6 months (eligible if receiving hormone therapy)

• Cancer‐free at the time of study enrolment

Exclusion criteria:

• Fear of aquatic exercise that would prevent participation in deep water running programme

Interventions

22 participants assigned to 8‐week exercise intervention:

• Land‐based exercise and deep water running (DWR) combined with education based on cognitive‐behavioural principles

• Each session was performed in groups of 8 to 10 participants and comprised 30 minutes of land‐based exercise followed by 20 minutes of DWR, with an additional 10 minutes of warm‐up and cool‐down time. Land‐based exercise included 15 minutes of full‐body mobility and 15 minutes of general strengthening exercises. Deep water running (cross‐country style) simulates running by using a flotation device in water levels over head height.

• From weeks 1 to 4, DWR workload corresponded to heart rate at 2 mmol of lactic acid. For weeks 5 to 8, workload was set at 3 mmol of lactic acid, based on pretest lactic acid values.

Adherence:

42 participants attended more than 80% of the 24 treatment sessions. Although 2 intervention participants reported ‘wake up tired in the morning’ after 1 session, this event did not impact programme completion and was not repeated.

22 participants assigned to control:

• Wait‐list control group

Outcomes

Primary outcome:

• Fatigue assessed by the PFS‐R

Other outcomes:

• Physical and mental general health via MOS SF‐12

• QoL via European Quality of Life 5 dimensions (EuroQoL‐5D) and European Visual Analogue Scale (EuroQoL‐VAS)

Numbers of participants assessed:

• Intervention: baseline, 22; post intervention, 22

• Control: baseline, 20; post intervention, 20

Adverse events: No further adverse events were associated with participation in the intervention.

Notes

Trial registration link: none available

Trial authors contacted: no

Intention‐to‐treat analysis: No missing data were reported.

Funding: not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Participants were allocated in order of arrival to complete each group.

Allocation concealment (selection bias)

High risk

Allocation was not concealed from researchers.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

“Assessor, who was blinded to participant group allocation”

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No missing data were reported.

Selective reporting (reporting bias)

Low risk

No selective reporting of outcomes is apparent.

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: single‐centre RCT

Number randomised: 108; 34 to exercise therapy, 36 to exercise placebo, 38 to control

Study start: January 2003; stop date: July 2005

Length of intervention: 8 weeks

Length of follow‐up: at 24 weeks

Country: UK

Participants

Age, years (mean SD):

• Exercise therapy group: 51.6 (8.8)

• Exercise placebo group: 50.6 (8.7)

• Control: 51.1 (8.6)

Stage:

• Exercise therapy: not reported

• Exercise placebo: not reported

• Control: not reported

Inclusion criteria:

• Women who were not regularly active

• Treated for localised breast cancer 12 to 36 months

• Aged 18 to 65 years

• Willing to attend supervised exercise sessions 3 times per week for 8 weeks

• Exercise pre‐contemplator, contemplator, or preparer as defined by the TTM

Exclusion criteria:

• Women with metastases

• Inoperable or active locoregional disease determined ineligible by clinician

• Physical or psychiatric impairment that would seriously influence physical mobility

• Nausea, anorexia, or other diseases affecting health

• High activity level

• Contraindication to exercise, assessed by Physical Activity Readiness

Interventions

34 participants assigned to 8‐week exercise intervention:

• Supervised one‐to‐one aerobic exercise performed 3 times per week for 50 minutes at moderate intensity (65% to 85% of age‐adjusted HR maximum and RPE of 12 to 13)

• In addition to exercise therapy, a variety of cognitive‐behavioural techniques for promoting exercise behaviour change were explored with participants during sessions.

36 participants assigned to exercise placebo:

• Exercise placebo group also attended 24 one‐to‐one 50‐minute sessions during 8 weeks; performed light‐intensity body conditioning/stretching (e.g. flexibility, passive stretching) exercises during which HR was maintained below 40% heart rate reserve (HR typically was kept below 100 beats per minute). No exercise counselling or behavioural change advice was provided; instead, conversations were centred on topics of everyday life (i.e. weather, news items, and families). Participants assigned to exercise placebo were otherwise asked to continue with their lifestyle as normal.

Adherence:

Attended at least 70% (at least 17 of 24 sessions) of sessions; exercise therapy group, 77%; exercise placebo group, 88.9%

38 participants assigned to control:

• No activity or education. Usual care group was asked to continue with their lives as usual.

Outcomes

Primary outcomes:

• FACT‐G

• FACT‐B

Secondary outcomes:

• Fatigue assessed with Revised PFS

• Satisfaction with life

• Depression assessed by BDI‐II

• Physical Self‐Perception Profile, including five 6‐item subscales: perceived sports competence, attractiveness of body, physical conditioning competence, physical strength competence, and physical self‐worth

• Physical activity and exercise behaviour assessed by asking participants how often they had participated in 1 or more physical activities for 20 to 30 minutes per session in the past 5 months and by completing the stage of change for exercise ladder (SOC)

• Aerobic fitness assessed via submaximal 8‐minute single‐stage walking test performed on a treadmill

• Weight and BMI

• Body fat assessed by bioelectrical impedance analysis

• Muscle function assessed by a Bioidex isokinetic machine

Numbers of participants assessed:

• Intervention: baseline, 34; at week 8, 33; at week 24, 31

• Exercise placebo: baseline, 36; at week 8, 36; at week 24, 34

• Control: baseline, 38; at week 8, 33; at week 24, 31

Adverse events: not reported

Notes

Trial registration link: none available

Trial authors contacted: yes, trial authors provided additional outcome data

Intention‐to‐treat analysis: unclear

Funding: Cancer Research UK (grant number: CE8304)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

“performed using stratified random permuted blocks”

Allocation concealment (selection bias)

Low risk

Telephone randomisations service was provided by an independent trials unit.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

“Outcome assessors were not blinded to participants’ group allocation”.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

“Data were analysed on an ITT basis”

It is unclear how this was done.

Selective reporting (reporting bias)

Low risk

No selective reporting of outcomes is apparent.

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: single‐centre RCT
Number randomised: 100; 36 to exercise begun during treatment (EE), 30 to exercise begun after treatment (CE), 34 to control
Study start and stop dates: 1999 to 2006
Length of intervention: 4 to 6 months
Length of follow‐up: at 1 year from baseline

Country: USA

Participants

Age, years (mean SD):

• Intervention (EE): 48.7 (8.4)

• Intervention (CE): 49.5 (9.5)

• Control: 51.6 (10.9)

Stage, n (%):

• Intervention (EE): stage I, 13 (39.4); stage II, 14 (42.4); stage III, 6 (48.2)

• Intervention (CE): stage I, 11 (39.3); stage II, 15 (53.6); stage III, 2 (7.1)

• Control: stage I, 14 (42.4); stage II, 13 (39.4); stage III, 6 (18.2)

Inclusion criteria:

• Women aged 18 years or older

• Confirmed diagnosis of breast cancer

• Beginning second cycle of chemotherapy

• Ability to read, write, and understand English

• Mentally able to understand and able to provide written informed consent

• Karnofsky Performance Scale (KPS) score > 60

Exclusion criteria:

• Receiving concurrent radiotherapy for another disease

• Had bone marrow transplantation

• Uncontrolled hypertension or diabetes mellitus

• Pain intensity rating ≥ 3 on a 0 to 10 numerical scale

• Lytic bone lesion or other orthopaedic limitations

• History of major depression or sleep disorders

• Chemotherapy in the past year

• Diagnosis of AIDS‐related malignancies or leukaemia

• Absolute contradictions to exercise testing as established by American College of Sports Medicine (1995)

Interventions

66 participants assigned to exercise intervention (36 to EE, 30 to CE):

• Individualised programme adjusted to participant’s fitness level and adjusted weekly to maintain the exercise prescription. Programme consisted of cardiovascular/aerobic exercise of participants' choice (e.g. walking, jogging, cycling) performed 3 to 5 times per week for 30 minutes at 2‐ to 14‐point intensity level (Borg scale, moderate exertion) over 4 to 6 months

30 participants assigned to control:

• Usual care; telephoned weekly by research nurse to enquire about their health

Adherence:

EE group reported adherence rate of 74% by end of intervention and 78% by end of follow‐up; CE group reported 86% adherence at end of intervention

Outcomes

No primary outcome stated:

• Physical activity questionnaire recorded self‐reported exercise activities, frequency, intensity, and duration

• Physical performance measured on Karnofsky Performance Status (KPS) scale

• Symptom checklist: list of 25 symptoms commonly experienced by individuals receiving chemotherapy. Format is a Likert‐type rating scale with descriptive anchors from 0 = none to 10 = terrible/awful

• Body composition via DEXA (fat mass, percent fat, lean body mass)

• Cardiorespiratory fitness assessed by maximal exercise testing

Outcomes measured:
• EE group: n = 36 at baseline, n = 36 at 4 to 6 months (end of intervention)
• CE group: n = 30 at baseline, n = 30 at 4 to 6 months (end of intervention)
• Control group: n = 34 at baseline, n = 34 at 4 to 6 months (end of intervention)

Adverse events: none reported

Notes

Trial registration link: none available

Trial authors contacted: no

Intention‐to‐treat analysis: no missing data evident in this study
Funding: National Cancer Institute; Clinical & Translational Science Institute, Clinical Research Center

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Generation of random sequence was not described.

Allocation concealment (selection bias)

Unclear risk

Whether treatment assignment was concealed from study personnel and participants was not described.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

"Measurements of study variables were taken by research nurses who were blinded to the participants' group assignment".

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No missing data were reported.

Selective reporting (reporting bias)

High risk

Data on cardiorespiratory fitness and on physical activity were not reported.

Other bias

High risk

Control group and intervention groups were reported as having similar activity levels as intervention groups post intervention, possible contamination. Low adherence rate of 74% by end of intervention and 78% at end of follow‐up in the intervention group

Methods

Study design: single‐centre RCT

Number randomised: 212; 106 to early exercise group (EEG), 106 to delayed exercise group (DEG)

Study start: not reported; stop date, not reported

Length of intervention: 4 weeks.

Length of follow‐up: at 6 to 8 weeks only in early exercise group

Country: South Korea

Participants

Baseline demographic and medical history variables for 32 in EEG and for 30 in DEG

Age, years (mean SD):

• EEG: 47.1 (8.5)

• DEG: 48.3 (8.2)

Stage, n (%):

• EEG: stage I, 3 (9.3); stage IIA, 13 (40.6); stage IIB, 12 (37.5); stage III, 4 (12.5)

• DEG: stage I, 2 (6.6); stage IIA, 15 (50.0); stage IIB, 10 (33.3); stage III, 3 (10.0)

Inclusion criteria:

• Not reported

Exclusion criteria:

• Evidence of recurrent disease or other musculoskeletal involvement such as low back pain, disc problems, osteoarthritis, rheumatoid arthritis, shoulder problems

Interventions

106 participants assigned to early exercise intervention:

• 40 minutes of aerobic exercise (40% to 75% of VO₂max) and 20 minutes of resistance exercise (9 different exercises of 2 sets of 8 to 12 repetitions at 60% to 80% of 1 repetition maximum for exercises of the extremities, or 5 to 10 repetitions for exercises of the axial muscles) 5 times a week over 4 weeks

Adherence: not reported

106 participants assigned to control:

• Delayed exercise group (DEG; n = 30) completed exercise programme from 4 to 8 weeks.

Outcomes

Outcomes:

• QoL evaluated based on European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ‐C30) (version 3) and EORTC QLQ‐BR23

• Cardiorespiratory function measured on the cycle test. Patients commenced cycling at 20 W and workload was increased by 25 W every minute. Test was completed when patients reached 85% of estimated maximal heart rate. Cardiorespiratory test score was assessed as power output that coincided with 85% maximal heart rate.

• Fatigue Severity Scale (FSS) consists of 9 questions responded to via a Likert scale ranging from 1 to 7, with lower scores meaning “disagreement” (greater disagreement with lower scores) and higher scores meaning “agreement” in the same fashion.

• Maximal isometric strength was assessed in 4 muscle groups bilaterally with a hand‐held digital dynamometer. Muscles assessed included elbow flexors, hip flexors, hip abductors, hip extensors, knee extensors, and knee flexors. Muscular groups were tested in the middle of the joint range.

Numbers of participants assessed:

• EEG: baseline, 32; at 2 weeks, 32; at 4 weeks, 32; at 6 weeks, 32; at 8 weeks, 32

• DEG: baseline, 30; at 2 weeks, 30; at 4 weeks, 30; at 6 weeks, 30; at 8 weeks, 30

Adverse events: not reported

Notes

Trial registration link: none available

Trial authors contacted: no

Intention‐to‐treat analysis: no

Funding: not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"1:1 ratio using a computer‐generated allocation sequence”

Allocation concealment (selection bias)

Unclear risk

Whether allocation was concealed was not reported.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not mentioned whether study personnel and outcome assessors were masked or blinded to study interventions

Incomplete outcome data (attrition bias)
All outcomes

High risk

Analysis performed only on “completers”; withdrawals not included in analysis.

Selective reporting (reporting bias)

Low risk

No selective reporting of outcomes is apparent.

Other bias

High risk

Dropout rate was high (71%).

Methods

Study design: single‐centre RCT

Number randomised: 36, 12 to aerobic interval training (AIT), 12 to continuous moderate training (CMT), 12 to control

Study start: February 2013; stop date: December 2014

Length of intervention: 6 weeks

Length of follow‐up: at 3 months for physical activity

Country: Canada

Participants

Age, years (mean SD):

• AIT: 56.2 (9)

• CMT: 56.3 (9)

• Control: 59.4 (9)

Stage, n (%):

• AIT: stage 0, 0 (0); stage I, 1 (3); stage II, 5 (15); stage III, 3 (9); other, 1 (3)

• CMT: stage 0, 1 (3); stage I, 2 (6); stage II, 2 (6); stage III, 5 (15); other, 1 (3)

• Control: stage 0, 1 (3); stage I, 4 (12); stage II, 2 (6); stage III, 3 (9); other, 0 (0)

Time since cancer diagnosis, mean years:

• AIT: 6

• CMT: 4

• Control: 7

Inclusion criteria:

• Completed different combinations of surgery, chemotherapy, radiation, and hormonal therapy for early‐stage breast cancer (stage I‐IIIA)

• Postmenopausal status was a set condition to minimise possible confounding factors associated with oestrogen status, treatment, and exercise response.

Exclusion criteria:

• Received diagnosis of metastatic disease, uncontrolled hypertension, history of cardiac disease, or pulmonary disease

• Did not receive approval from physician to participate

• Age > 75 years

• BMI> 40 kg/m²

• Could not commit to 18 exercise sessions in 6 weeks

• Any other contraindications to exercise

Interventions

23 participants assigned to 1 of 2 exercise interventions:

• AIT group was prescribed an interval programme that started with 2 weeks of introductory intervals at a maximal intensity of 80% VO₂peak, followed by progressively higher intensity interval bouts of 3 supervised sessions per week for 4 weeks, eventually requiring 2‐minute efforts that would elicit close to maximal effort.

• CMT was prescribed a continuous, moderate‐intensity aerobic protocol. Depending on baseline fitness and experience, individuals completed 3.22 km (2 miles) at initial intensity of 55% to 60% VO₂peak for 3 supervised sessions per week. By end of week 5, individuals progressed to 4.02 km (2.5 miles) at 70% VO₂peak (6‐week intervention).

• Exercise sessions were matched by ensuring a set distance was covered at each session, starting with a minimum of 3.22 km and progressing to 4.02 km by week 5 (2 to 2.5 miles).

Adherence:

CMT group (n = 11) completed 17.8 sessions that took an average of 40 minutes to complete and covered a total distance of 65.34 km. AIT group (n = 12) completed 17.8 high‐intensity interval sessions in average time of 36 minutes and covered a total distance of 64.86 km. At 3 months, 92% of women in the AIT group reported achieving or superseding the recommended weekly exercise dose according to guidelines. Only 42% of individuals in the CMT group reported meeting the recommended dose.

10 participants assigned to control:

• Control group was offered a delayed exercise intervention. Exercise volume in the control group was not officially tracked. All participants were asked to maintain their current normal dietary habits and daily activities for the 6‐week duration. If individuals deviated from their current habits, they were asked to report changes at endpoint.

Outcomes

Primary outcomes:

• VO₂max via maximal incremental cardiopulmonary exercise protocol and expired gases analysed via the TrueOne 2400 metabolic cart (Parvo Medics Inc., Sandy, UT)

Secondary outcomes:

• Weight (kg)

• Hip circumference (cm)

• Resting heart rate (RHR) noted after 5 minutes of seated silence

• Muscle strength 1RM assessed on the leg press. Maximum weight and number of repetitions used to estimate 1 repetition

• Insulin measured by the Siemens Immulite 2500 (Siemens Healthcare Diagnostics, Newark, DE, USA)

• Glucose measured via Siemens ADIVA 1800 (Siemens Healthcare Diagnostics, Newark, DE, USA)

• CRP measured on Siemens BNII (Siemens Healthcare Diagnostics, Newark, DE, USA)

• Homeostatic Model Assessment (HOMA)‐insulin resistance

Numbers of participants assessed:

• AIT: baseline, 12, at 6 weeks, 12

• CMT: baseline, 12; at 6 weeks, 11

• Control: baseline, 12; at 6 weeks, 10

Adverse events: No adverse events occurred during supervised exercise sessions or were self‐reported by participants.

Notes

Trial registration link: none available

Trial authors contacted: no

Intention‐to‐treat analysis: no

Funding: BC Sports Medicine Research Foundation

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

“Randomly assigned”; method of randomisation not reported

Allocation concealment (selection bias)

Unclear risk

Whether allocation was concealed was not reported.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not mentioned whether study personnel and outcome assessors were masked or blinded to study interventions

Incomplete outcome data (attrition bias)
All outcomes

High risk

Analysis performed only on “completers”; withdrawals not included in analysis

Selective reporting (reporting bias)

Low risk

No selective reporting of outcomes is apparent.

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: multi‐centre RCT

Number randomised: 422; 109 to cognitive‐behavioural therapy (CBT); 104 to physical exercise; 106 to CBT and physical exercise combined; 103 to control group

Study start: January 2008; recruitment stop date: December 2009

Length of intervention: 12 weeks

Length of follow‐up: at 6 months (at 3 months post intervention)

Country: Netherlands

Participants

Age, years (mean SD):

• CBT: 48.2 (5.7)

• Exercise: 47.7 (5.6)

• CBT + Exercise: 49.0 (4.9)

• Control: 47.8 (6.0)

Stage:

• Stages: T1‐4, N0‐1, and M0 (i.e. stage I‐IIIC)

Inclusion criteria:

• Primary breast cancer (stages T1‐4, N0‐1, and M0)

• Younger than 50 years and premenopausal at diagnosis

• Had received adjuvant chemotherapy and/or hormonal therapy

• Disease‐free at study entry

• Reported at least a minimal level of menopausal symptoms

• Chemotherapy had to be completed at least 4 months before but not more than 5 years before study entry (hormonal therapy could still be ongoing)

Exclusion criteria:

• Lack of basic proficiency in Dutch

• Serious cognitive or psychiatric problems

• Serious physical comorbidity

• Obesity (body mass index > 35), because exercise may be contraindicated as a treatment for hot flashes in obese women

• Participating in concurrent studies targeted at menopausal symptoms or involving similar interventions

Interventions

109, 104, and 106 participants were assigned to CBT, exercise and CBT, and exercise 12‐week intervention, respectively:

• CBT consisted of 6 weekly group sessions of 90 minutes each and 1 booster session 6 weeks post completion, including relaxation exercises. The primary focus of CBT was on hot flashes and night sweats, but other symptoms (e.g. vaginal dryness) and problem areas (such as body image, sexuality, and mood disturbance) were also addressed.

• The aerobic exercise programme was an individually tailored, home‐based, self‐directed exercise programme of 2.5 to 3 hours per week. During the intake session, the physiotherapist assisted each woman in selecting an appropriate form of exercise (e.g. swimming, running, cycling). Each woman was provided with a heart rate monitor and was instructed in its use to achieve a target heart rate (60% to 80% Karvonen). During weeks 4 and 8, women had telephone interviews with the physiotherapist to discuss their experiences and possible need to adjust the programme. During the last week, women visited the clinic for a final session, during which they received advice on how best to maintain their desired level of physical activity.

• Women in the combined intervention group underwent CBT and exercise programmes concurrently.

Adherence:

• Fifty‐eight per cent of the CBT group, 64% of the PE group, and 70% of the CBT and exercise group did not meet criteria for compliance (i.e. at least 4 of 6 CBT sessions and/or minimum of 24 PE training sessions, with an average of 3 kCals/kg or 6.45 METs per session).

103 participants assigned to control:

• Wait‐list control: On completion of the study, control group participants could choose to undergo the CBT or PE programme.

Outcomes

Primary outcomes:

• Endocrine symptoms assessed by the 18‐item endocrine subscale of the Functional Assessment of Cancer Therapy questionnaire (FACT‐ES)

• Hot flashes and night sweats (HF/NS) assessed by the Hot Flush Rating Scale. The Hot Flush Rating Scale comprised 2 items measuring frequency of hot flashes and night sweats (HF/NS frequency rating) and 3 items measuring the extent to which these symptoms were perceived to be problematic and interfered with daily life (HF/NS–problem rating).

Secondary outcomes:

• Sexual functioning assessed by the Sexual Activity Questionnaire (SAQ)

• Urinary symptoms assessed by the 5‐item incontinence scale of the Bristol Female Lower Urinary Tract Symptoms Questionnaire (BFLUTS)

• Body image assessed by the 4‐item QLQ‐BR23 subscale

• Psychological distress assessed by the 14‐item Hospital Anxiety and Depression Scale (HADS)

• Generic HRQoL assessed by the MOS SF‐36, which includes 8 subscales as well as physical and mental component scores

• Program compliance assessed via session attendance records for CBT participants and number and intensity of training sessions, as recorded by the heart rate monitor, for PE participants. Participants were considered to be compliant if they attended at least 4 of 6 CBT sessions and/or had a minimum of 24 PE training sessions, with an average of 3 kCals/kg per session (or 6.45 METs).

Numbers of participants assessed:

• CBT: baseline, 109; at 12 weeks, 86; at 6 months, 88

• Exercise: baseline, 104; at 12 weeks, 87; at 6 months, 79

• CBT + Exercise: baseline, 106; at 12 weeks, 90; at 6 months, 89

• Control: baseline, 103; at 12 weeks, 89; at 6 months, 84

Adverse events: not reported

Notes

Trial registration link: https://clinicaltrials.gov/ct2/show/NCT00582244

Trial authors contacted: no

Intention‐to‐treat analysis: no

Funding: supported by grant No. NKI 2006‐3470 from the Dutch Cancer Society; the Integral Cancer Center, Amsterdam; the Pink Ribbon Foundation; and Polar Electro Nederland

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

“Computerized block randomization”

Allocation concealment (selection bias)

Unclear risk

Whether treatment assignment was concealed from study personnel and participants was not described. Centralised randomisation was not mentioned.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No mention of whether study personnel and outcome assessors were masked or blinded to study interventions

Incomplete outcome data (attrition bias)
All outcomes

High risk

“Missing values were replaced by the average score of the completed items in the same scale for each individual, provided that at least 50% of the items in that scale had been completed”.

Selective reporting (reporting bias)

Low risk

No selective reporting of outcomes is apparent.

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: single‐centre RCT

Number randomised: 60; 20 to supervised exercise, 20 to home exercise, 20 to control

Study start: not reported; stop date: not reported

Length of intervention: 12 weeks

Length of follow‐up: to end of intervention

Country: Turkey

Participants

Age, years (mean SD):

• Supervised exercise: 49.7 (8.3)

• Home exercise: 55.1 (6.9)

• Control: 50.3 (10.4)

Stage, n (%):

• Not stated but recurrent or progressing breast cancer excluded

Inclusion criteria:

• Completion of surgical therapy, radiation therapy, and chemotherapy

• Postmenopausal

• Not smoking in the past year

• Agreeing to participate in the study

• Absence of any physical condition that would prevent exercising

• Having the cognitive capacity to answer the questions

Exclusion criteria:

• Recurrent or progressing breast cancer, lymphoedema, serious cardiac disease or unregulated hypertension, acute or chronic respiratory disease, mental disease, any infection, any immune or endocrinological disorder that would alter immune indicators, rheumatic disease, serious musculoskeletal disease (that would hinder exercising)

• Loss of more than 10% of body weight in the past 6 months

• Attended a regular exercise programme in the past 6 months

Interventions

40 participants assigned to two 12‐week exercise interventions:

• Supervised exercise group performed aerobic exercise + resistive exercise for 45 minutes/d for 3 days/week and brisk walking for 30 minutes/d for 3 days/week. Exercise programme comprised 10 minutes of warming, breathing exercise, upper and lower limb resistive exercises with Theraband set at moderate resistance, and semi‐squatting periods. Warming exercise comprised brisk walking, rhythmical range‐of‐motion exercises, repeated 10 times, for upper and lower limb joints; cool‐down exercises comprised breathing, stretching (shoulder and pectoral muscles, gastrocnemius‐soleus, flexors and rotators of the hip, back muscles) and relaxation exercises.

• Home exercise group performed brisk walking for 30 minutes/d for 3 days/week. Participants in groups 1 and 2 were taught how to measure their heart rate and maximal heart rate for age calculated to establish pace of walking.

• All participants were given a 30‐minute education regarding adverse effects of breast cancer, prevention of lymphoedema, and related activities, and were given a patient information booklet that included lymphoedema‐specific exercises.

Adherence: No data on adherence were reported.

20 participants assigned to control:

• Participants received only the education programme mentioned above.

Outcomes

Primary outcomes:

• Angiogenesis and apoptosis‐related molecules including interleukin‐6, interleukin‐8, tumour necrosis factor alpha, epithelial neutrophil activating protein‐78, platelet‐derived growth factor, vascular endothelial growth factor, growth‐related oncogene alpha, regulated upon activation, normal T cell, thrombopoietin, angiogenin, oncostatin M, and monocyte chemotactic proteins 1, 2, and 3

Secondary outcomes:

• HRQoL via EORTC QLQ‐C30

• Fatigue assessed via the Brief Fatigue Inventory (BFI)

• Depression via the BDI

Numbers of participants assessed:

• Supervised exercise: baseline, 20; at 12 weeks, 20

• Home exercise: baseline, 20; at 12 weeks, 18

• Control: baseline, 20; at 12 weeks, 20

Adverse events: No participants experienced any side effects or developed lymphoedema (although 1 participant developed metastasis).

Notes

Trial registration link: none available

Trial authors contacted: no

Intention‐to‐treat analysis: unclear

Funding: supported by Ege University Medical Faculty BAP project (Project Number: 2010‐TIP‐069)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Using random numbers table

Allocation concealment (selection bias)

Unclear risk

Whether treatment assignment was concealed from study personnel and participants was not described.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

“Molecular biologists that performed the measurements and the oncology specialist who made the assessment were blind to the exercise groups of the patients”.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Missing data handling methods were not reported.

Selective reporting (reporting bias)

Low risk

No selective reporting of outcomes is apparent.

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: single‐centre RCT

Number randomised: 94; 48 to intervention group, 46 to control group

Study start: not reported; stop date: not reported

Length of intervention: 4 weeks

Length of follow‐up: at 3 months

Country: Canada

Participants

Age, years (mean SD):

• Intervention: 53.09 (9.65)

• Control: 51.84 (10.25)

Stage, n (%):

• Intervention: stage 0, 2 (4.5); stage I, 21 (47.7); stage II, 18 (40.9); stage III, 3 (6.8)

• Control: stage 0, 4 (9.3); stage I, 17 (39.5); stage II, 12 (27.9); stage III, 10 (23.3)

Inclusion criteria:

• Diagnosis of initial non‐metastatic breast cancer

• Completion of initial breast cancer treatment no longer than 2 years before enrolment

• Receipt of 1 series of adjuvant treatments of radiation therapy, or had received radiation therapy in combination with other adjuvant treatments (e.g. chemotherapy, hormonal therapy)

• Ability to understand and speak French

• Residence near the cancer centre

• Availability to take part in a series of 4 weekly sessions

• Acceptance of randomisation procedure pass revised Physical Activity Readiness Medical Examination

• Authorisation of supervising physician before performing fitness assessment

Exclusion criteria:

• Clinical levels of depression symptoms, as measured by HADS (score > 10)

• Insomnia, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition

• Any symptom of cancer recurrence

• Known severe health problems other than cancer

Interventions

48 participants assigned to exercise intervention:

• 4 weekly group meetings of 2.5 hours and 1 short telephone booster session (5 to 15 minutes)

• 1 hour devoted to supervision of walking training by a kinesiologist or a trained research nurse

• 1.5 hours devoted to psychoeducational fatigue management sessions

Adherence:

• 45 of 48 participants completed the full treatment

Co‐intervention: psychoeducational fatigue management

46 participants assigned to control:

• Normal activity

Outcomes

Primary outcome:

• Fatigue measured by General/Physical Fatigue subscale of the MFSI

Other outcomes:

• Cardiorespiratory fitness measured as submaximal oxygen consumption, estimated from single‐stage treadmill walking test

• QoL measured with MOS SF‐12

• Energy level measured via the vigour subscale of the shortened POMS

• Anxiety and depression measured on the POMS

Numbers of participants assessed:

• Intervention: baseline, 48; at 4 weeks, 45; at 3 months, 45

• Control: baseline, 46; at 4 weeks, 43; at 3 months, 43

Adverse events: cancer recurrence: 2 in exercise group, 1 in control group

Notes

Trial registration link: none available

Trial authors contacted: no

Intention‐to‐treat analysis: no

Funding: Fonds de Recherche en Sante du Quebec, Investigator Award

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Sequence of randomisation was “computer generated”.

Allocation concealment (selection bias)

Unclear risk

“Sealed envelopes, which were concealed to both kinesiologist and patient”; no mention of whether they were sequential or opaque

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Study personnel and outcome assessors were not masked or blinded to study interventions.

Incomplete outcome data (attrition bias)
All outcomes

High risk

Four participants from the exercise group were not included in the analyses (withdrew, n = 1; cancer recurrence, n = 2; metastatic breast cancer diagnosis, n = 1); 3 participants from the control group were not included in the analyses (withdrew, n = 2; cancer recurrence, n = 1).

Selective reporting (reporting bias)

Low risk

No selective reporting of outcomes is apparent.

Other bias

Low risk

Trial appears to be free of other problems that could put it at high risk of bias.

Methods

Study design: RCT

Number randomised: 26 total; 16 to an exercise intervention, 10 to a control

Study start: March 2010; stop date: January 2011

Length of intervention: 8 weeks

Length of follow‐up: at 3 months post intervention

Country: Ireland

Participants

Age, years (mean SD):

• Intervention: 50.05 (8.27)

• Control: 45.05 (9.04)

Stage, n (%):

• Intervention: stage I, 3 (18.8); stage II, 10 (62.6); stage III, 3 (18.8)

• Control: stage I, 4 (40.0); stage II, 3 (30); stage III, 3 (30)

Inclusion criteria:

• Breast cancer survivors who had consented to the PEACH trial

• Completion of adjuvant chemotherapy or radiotherapy with curative intent within the preceding 2 to 6 months

• Receipt of neoadjuvant chemotherapy or chemoradiotherapy followed by surgery

• Continuing onto adjuvant hormone therapy and anti‐Her2 directed therapy

• Ability to understand English

• Willingness to be randomised

• Medical clearance to exercise

• Aged 21 to 69

Exclusion criteria:

• Evidence of active cancer

• Chronic medical and orthopaedic conditions that would preclude exercise (e.g. uncontrolled congestive heart failure or angina, recent MI, breathing difficulties requiring oxygen use, hospitalisation)

• Taking beta‐blocker medication

• Prior history of another cancer in previous 5 years (exceptions: non‐melanoma skin cancer, non‐invasive cancer of the cervix)

• Confirmed pregnancy

• Dementia or psychiatric illness that would preclude ability to participate in study

• Incomplete haematological recovery after chemotherapy (WCC < 3, Hb < 10, or platelets < 100)

• BMI > 35

• LVEF post chemotherapy < 50% or > 20% deterioration of baseline compared with LVEF before systemic treatment

Interventions

16 participants assigned to exercise intervention:

• Twice‐weekly supervised aerobic intervention and a home exercise programme for 8 weeks. Participants rotated between 3 aerobic exercise stations during the class (stationary bike, treadmill, rowing ergometer). Participants with “poor” fitness started the intervention at an intensity range of 35% to 55% heart rate reserve (HRR), participants with “fair” fitness started at 40% to 60% HRR, and those classified as “average” commenced at 45% to 65%HRR. Aerobic intensity zones were progressed by 5% HRR every 2 weeks. Duration of individual sessions was 21 minutes in week 1, progressed to 42 minutes in week 8 (3‐minute increase every 2 weeks alternate with intensity increase).

Adherence: 6/16 (37.5%) adhered to < 90% of the exercise class but completed follow‐up assessments.

10 participants assigned to control:

• Did not engage in a structured exercise programme but were offered an exercise advice session following final assessment

Outcomes

Outcomes:

• Body composition including body weight estimated by a bioimpedance analyser (Tanita MC 180 MA Multi‐Frequency Body Composition Analyzer; Tanita Corp., Tokyo, Japan)

• Waist circumference measured at midpoint between top of the iliac crest and last rib

• Resting blood pressure measured by the auscultatory method following a 5‐minute rest period. Blood pressure measurements were taken on the non‐surgical side, in duplicate, and averaged for data entry.

• Venous blood samples taken to measure glucose, insulin, lipid profile (TC), HDL‐C, LDL‐C and triglycerides, glycosylated haemoglobin levels (HBA1c), and CRP. Insulin resistance was calculated via HOMA: [(fasting glucose (mmol/L) × fasting insulin (mU/L))/22.5]

• Metabolic syndrome diagnosed in the presence of any 3 of the following: elevated waist circumference (≥ 80 cm); elevated triglycerides (≥ 1.7 mmol/L) or drug therapy for lipid abnormalities; reduced HDL‐C (< 1.3 mmol/L) or drug therapy for lipid abnormalities; elevated blood pressure (systolic ≥ 130 mmHg and/or diastolic ≥ 85 mmHg) or antihypertensive medication; elevated fasting glucose (≥ 100 mg/dL) or glucose‐lowering medication

• Physical activity measured objectively with the triaxial RT3 activity monitor (Stayhealthy Inc., Montrovia, CA, USA). Participants wore the monitor for 7 days, during waking hours, following each assessment.

• Physical activity measured subjectively with the Godin Leisure Time Exercise Questionnaire, which records the frequency of strenuous, moderate, and mild exercise bouts of at least 15 minutes' duration

• Estimated dietary record (Medical Research Council, UK) prepared by participants. Diaries were analysed via WISP (Tinuveil Software, Llanfechell, Anglesey, UK) nutrition analysis programme.

Numbers of participants assessed:

• Intervention: baseline, 8 weeks, and 3 months post intervention, 16 (except total and HDL‐C, TC:HDL ratio, triglycerides, glucose, and HBA1c); 15 (LDL‐C, insulin); HOMA, 14

• Control: baseline, 8 weeks, and 3 months post intervention, 10 (except LDL‐C, insulin, HOMA, HBA1c, sedentary activity, light‐, moderate‐, and vigorous‐intensity activity); 9

Adverse events: not reported

Notes

Trial registration link: https://clinicaltrials.gov/ct2/show/NCT01030887

Trial authors contacted: no

Intention‐to‐treat analysis: yes, but LOCF used

Funding: not reported

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random numbers list

Allocation concealment (selection bias)

Unclear risk

Whether allocation was concealed was not reported.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Owing to the nature of the intervention, it was not possible to conceal allocation to the intervention from participants.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

“Assessments were completed by the same researcher at every visit who was blinded to the participants’ group assignment”.

Incomplete outcome data (attrition bias)
All outcomes

High risk

LOCF procedure was used for missing variables.

Selective reporting (reporting bias)