Winters‐Stone 2011.

Methods	Study design: single‐centre RCT Number randomised: 106; 52 to intervention, 54 to control Study start: October 2006; stop date: January 2009 Length of intervention: 12 months Length of follow‐up: to end of intervention Country: USA
Participants	Age, years (mean SD): Intervention: 63.3 (6.7) Control: 62.2 (6.7) Stage, n (%): Intervention: stage 0, 4 (7.7); stage I, 20 (38.5); stage II, 25 (48.1); stage IIIA, 1 (1.9); not reported, 2 (3.8) Control: stage 0, 2 (3.7); stage I, 22 (40.7); stage II, 19 (35.2); stage IIIA, 5 (9.3); not reported, 6 (11.1) Inclusion criteria: • Diagnosis of stage 0–IIIA breast cancer at or after age 50 • Postmenopausal • ≥ 1 year post chemotherapy or radiotherapy • Non‐osteoporotic • No bone‐altering medication other than adjuvant hormone therapy • Physician clearance to exercise • No regular participation in resistance and/or impact exercise (fewer than two 30‐minute sessions per week) in the past month • Physical and cognitive ability to complete study testing Exclusion criteria: • None reported
Interventions	52 participants assigned to 1‐year exercise intervention: Resistance plus impact intervention (POWIR: Prevent Osteoporosis With Impact + Resistance) used in this study complied with American College of Sports Medicine (ACSM) recommendations for preserving bone health in postmenopausal women by using resistance and/or impact exercise at moderate‐to‐high bone‐loading forces. Resistance training at loads corresponding to 60% to 70% of 1RM for 1 to 3 sets of 8 to 12 repetitions to build lean mass and strength in novice weight lifters and older adults. Free weights were used to apply resistance—dumbbells for upper body, weighted vests for lower body, and a barbell for 1 combined upper + lower body exercise. Impact exercise consisted of 2‐footed jumps from the ground to a target height 1″ from the floor with a bent‐knee landing, performed with weighted vests on and in sets of 10. During a single exercise session, participants warmed up, performed 1 to 6 jump sets, 1 to 2 sets of 3 to 4 upper body exercises, and 3 to 4 lower body exercises, then cooled down. Home exercises were similar to those performed in the supervised class, except that resistance bands replaced free weights for upper body exercises, and lower body exercises were performed without weighted vests. Adherence: Total average attendance: intervention, 57%; control, 62% Supervised‐only average attendance: intervention, 76%; control, 72% Home‐only average attendance: intervention, 23%; control, 44% 54 participants assigned to control: Progressive low‐intensity stretching, 3 times per week for 1 year Participants performed a series of whole body stretching and relaxation exercises in a seated or lying position. Selected exercises were chosen to minimise weight‐bearing forces, so that little stimulus to the musculoskeletal system was applied and energy expenditure was minimal.
Outcomes	Primary outcomes: Bone mineral density of hip and spine via DEXA Biomarkers of blood turnover; serum osteocalcin (ng/mL) and urinary deoxypyridinoline cross‐links (nmol/mmolCr) by ELISA Other outcomes: Body weight and body composition assessed via DEXA Habitual physical activity measured with the CHAMPS physical activity questionnaire for older adults (kcal/day in all activities) Habitual calcium (dietary + supplemental) Total energy intake assessed with the 2005 Block Food Frequency Questionnaire Numbers of participants assessed: Intervention: baseline, 52; at 6 months, 33; at 12 months, 36 Control: baseline, 54; at 6 months, 32; at 12 months, 31 Adverse events: No adverse effects were associated with participation in either group.
Notes	Trial registration link: https://clinicaltrials.gov/ct2/show/NCT00591747 Trial authors contacted: no Intention‐to‐treat analysis: yes, but data were available only for per‐protocol analyses Funding: Susan G. Komen Race for the Cure and the National Cancer Institute; partial support from the Oregon Clinical and Translational Research Institute (OCTRI), National Center for Research Resources (NCRR) ‐ a component of the National Institutes of Health (NIH) ‐ and NIH Roadmap for Medical Research
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Generation of the random sequence was not described
Allocation concealment (selection bias)	High risk	“Group assignments were placed in sealed, sequentially numbered envelopes and opened by the participant following the completion of baseline testing”. Envelopes were not 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	Low risk	“Trained technicians blinded to group assignment” carried out testing.
Incomplete outcome data (attrition bias) All outcomes	High risk	The intent‐to‐treat (ITT) analysis was performed via hierarchical linear modelling. However, although inferences were based on ITT analyses, data were available only for per‐protocol analyses (in table format). High attrition rate was reported in the intervention group.
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.

1RM: 1‐repetition maximum.

7‐DPAR: 7‐day physical activity recall questionnaire.

ACSM: American College of Sports Medicine.

AIDS: acquired immunodeficiency syndrome.

AIT: aerobic interval training.

API: Aerobic Power Index.

BCE: Bone Collagen Equivalents.

BCPT: Breast Cancer Prevention Trial.

BDI: Beck Depression Inventory.

BES: Body Esteem Scale.

BFLUTS: Bristol Female Lower Urinary Tract Symptoms Questionnaire.

BIQ: Body Image Questionnaire.

BIS: bioimpedance spectroscopy.

BMI: body mass index.

BPI: Brief Pain Inventory.

BPNS: Basic Psychological Needs Satisfaction Scale.

BREQ‐2: Behavioral Regulation for Exercise Questionnaire‐2.

BRI: bone remodelling index.

BSAP: bone‐specific alkaline phosphatase.

CARES‐SF: Cancer Rehabilitation Evaluation System Short Form.

CBT: cognitive‐behavioural therapy.

CCS: Canadian Cancer Society.

CE: exercise begun after treatment.

CES‐D: Centers for Epidemiological Studies—Depression Scale.

CHAMPS: Community Health Activities Model Program for Seniors.

CI: confidence interval.

CMT: continuous moderate training.

COM: combination of print material and pedometers intervention.

CP: chemotactic protein.

CRP: C‐reactive protein.

CTACK: cutaneous T cell‐attracting chemokine.

DASH: Disability of the Arm, Shoulder, and Hand questionnaire.

DASS‐21: Depression and Anxiety Stress Scale‐21.

DCIS: ductal carcinoma in situ.

DEG: delayed exercise group.

DEXA: dual‐energy X‐ray absorptiometry.

DWR: deep water running.

ECOG: Eastern Cooperative Oncology Group.

EE: exercise begun during treatment.

EEG: early exercise group.

ELISA: enzyme‐linked immunosorbent assay.

EORTC QLQ‐BR23: European Organization for Research and Treatment of Cancer core quality of life questionnaire.

EORTC QLQ‐C30: European Organization for Research and Treatment of Cancer core quality of life questionnaire: breast cancer‐specific module.

EuroQoL‐5D: European Quality of Life 5 dimensions.

EuroQoL‐VAS: European Quality of Life visual analogue scale.

FACIT‐F: Functional Assessment of Chronic Illness Therapy ‐ Fatigue.

FACT: Functional Assessment of Cancer Therapy.

FACT‐B: Functional Assessment of Cancer Therapy ‐ Breast.

FACT‐Cog: Functional Assessment of Cancer Therapy ‐ Cognitive.

FACT‐ES: Functional Assessment of Cancer Therapy ‐ Endocrine Subscale.

FACT‐F: Functional Assessment of Cancer Therapy ‐ Fatigue.

FACT‐G: Functional Assessment of Cancer Therapy ‐ General.

FFQ: Food Frequency Questionnaire.

FGF: fibroblast growth factor.

FSI: Fatigue Symptom Inventory.

FSS: Fatigue Severity Scale.

G‐CSF: granulocyte colony‐stimulating factor.

gmCSF: granulocyte‐macrophage colony‐stimulating factor.

GRO: growth‐related oncogene.

HADS: Hospital Anxiety and Depression Scale.

HbA1c: glycosylated haemoglobin.

HDL‐C: high‐density lipoprotein cholesterol.

HF/NS: hot flashes and night sweats.

HGF: hepatocyte growth factor.

HLRE: high‐load resistance exercise.

HMWA: high‐molecular‐weight adiponectin.

HOMA: homeostatic model assessment.

HR: heart rate.

HRmax: maximum heart rate.

HRR: heart rate reserve.

IBCSG: International Breast Cancer Study Group.

ICAM: intercellular adhesion molecule.

IFN: interferon.

IGF: insulin‐like growth factor.

IGFBP: insulin‐like growth factor binding protein.

IL: interleukin.

IP: inducible protein.

IPAQ: International Physical Activity Questionnaire.

ITT: intention‐to‐treat.

KPS: Karnofsky Performance Status.

LDL‐C: low‐density lipoprotein cholesterol.

LIF: leukaemia inhibitory factor.

LLRE: low‐load resistance exercise.

LOCF: last observation carried forward.

LPS: lipopolysaccharide.

LSI: Leisure Score Index; Life Satisfaction Inventory.

LVEF: left ventricular ejection fraction.

MCS‐F: macrophage colony‐stimulating factor.

MET‐h: metabolic equivalent hours.

METs: metabolic equivalents.

MFI: Multi‐dimensional Fatigue Inventory.

MFSI: Multi‐dimensional Fatigue Symptom Inventory.

MFSI‐SF: Multi‐dimensional Fatigue Symptom Inventory Short Form.

MI: myocardial infarction.

MIG: monokine induced by IFNγ.

MIP: macrophage inflammatory protein.

MOS SF‐36: Medical Outcomes Study Short Form‐36.

MVPA: moderate‐vigorous physical activity.

NCI: National Cancer Institute.

NCIC: National Cancer Institute of Canada.

NGF: nerve growth factor.

NK: natural killer.

NKCA: natural killer cell activity.

NTx: N‐terminal telopeptide.

NYHA: New York Heart Association.

PA: physical activity.

PAL: physical activity log.

PANAS: Positive and Negative Affect Scale.

PDGF: platelet‐derived growth factor.

PE: physical education.

PED: pedometer intervention.

PFS: Piper Fatigue Scale.

PFS‐R: Revised Piper Fatigue Scale.

PHA: phytohemagglutinin.

PM: print material.

POMS: Profile of Mood States.

PPO: peak power output.

pQCT: peripheral quantitative computed tomography.

PROMIS: Patient Reported Outcomes Measurement Information System.

PSQI: Pittsburgh Sleep Quality Index.

QLQ‐BR23: quality of life questionnaire: breast cancer‐specific module.

QoL: quality of life.

RCT: randomised controlled trial.

RER: respiratory exchange ratio.

RM: repetition maximum.

RPE: rate of perceived exertion.

RSE: Rosenberg Self‐Esteem Scale.

RTR: reach‐to‐recovery.

SAQ: Sexual Activity Questionnaire.

SCF: stem cell factor.

SCGF: stem cell growth factor.

SCL‐90R: Symptom Checklist‐90 Revised.

SCT: social cognitive theory.

SD: standard deviation.

SDF: stromal cell‐derived factor.

SOC: stage of change.

SPAS‐7: Social Physique Anxiety Scale‐7.

STAI: State‐Trait Anxiety Index.

TC: total cholesterol.

TCC: Tai Chi Chuan.

TG: triglyceride.

TNF: tumour necrosis factor.

TOI: Trial Outcome Index.

TRAIL: tumour necrosis factor‐related apoptosis‐inducing ligand.

TTM: Transtheoretical model.

URCC SI: University of Rochester Cancer Center Symptom Inventory.

VCAM: vascular cell adhesion molecule.

VE/VCO₂: minute ventilation carbon dioxide production relationship.

VE/VO₂: minute ventilation oxygen production relationship.

VEGF: vascular endothelial growth factor.

VE_peak: peak ventilation.

VO₂max: maximal oxygen uptake.

VO₂peak: peak oxygen uptake.

WCC: white cell count.

WHO: World Health Organization.

WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index.

YMCA: Young Men's Christian Association.

YOCAS: yoga intervention based on gentle Hatha and restorative yoga.