Study, Year, Country Study design Participants Intervention Outcomes Assessment time points Results Author’s conclusion Khan et al, 2012 Australia RCT N = 85. treatment group = 43 and control = 42 (loss to follow-up 6) Inclusion criteria: aged >18 years; confirm BC diagnosis, currently disease free and assessed by a surgeon/oncologist Exclusion: survival less than 4 months, severe disease and unable to participate in the programme. Treatment group – ambulatory individualized high intensity MD programme (Social, Psychology, OT, PT and medicine) 3 one-hour sessions of interrupted therapy/week, for 8 weeks Control group – usual activity at home (local gym, yoga, community activities) and received fortnightly phone calls DASS,  PIPP, CARES-SF, FIM Pre-intervention (baseline) and 4 months post intervention • Significant difference between both groups in improved at 4 months for DASS Depression scores (p=0.006) (moderate effect size, r>0.3), PIPP Mobility (p=0.05) and Participation (p=0.04) scales, and CARES-SF Global score (p=0.02) (small effect size, r< 0.3).  • Treatment group, compared with control group, showed significant improvement in the DASS Depression scores:  22/42 (52.4%) versus 12/37 (32.4%) (p=0.02). • No difference between groups was noted in the FIM scale. Rehabilitation can benefit participation in BC survivors.  Evidence for specific rehabilitation interventions is needed. Integrated cancer programmes allow opportunities to evaluate patients in various settings, but require outcome research to develop service models for survivorship issues. Cho et al, 2006 South Korea RCT N = 65. treatment group = 34 and control = 31 Inclusion criteria: histologically confirmed stages of BC, no current progressive disease; within 2 years after the mastectomy; completion of chemotherapy and/or radiotherapy with or without current hormone therapy Exclusion: any mental disease or systemic disease Treatment group - ambulatory MD rehabilitation programme (psychology based education, exercise, peer- support group activity, medical input, dietician, image consultant, fitness instructor) for 3 episodes/sessions per week for 10 weeks Control group – wait-list no treatment (offered treatment post study) ROM shoulder, Psychological Adjustment Scale, and a local quality-of life measure Pre-intervention (baseline) and 10 weeks post intervention At 10 weeks follow-up: • Affected shoulder joint ROM significantly increased in the intervention group (11.5 % vs. 1.3%, p=0.000). • Significant increase in the flexion in both intervention and control group. Compared to the control group, there was significant differences in extension, abduction, external rotation, and internal rotation after the test in the intervention group (p=0.000, p=0.011, p=0.006, p=0.000, respectively). • Psychosocial adjustment in the intervention group increased by 2.9 points while it decreased in the control group by 3.0 points (p=0.000). • QoL in the intervention group increased by 0.9 points while it decreased in the control group by 0.1 points (p=0.002). A comprehensive group rehabilitation programme, comprised of psychology-based education, exercise and peer support group activity promote the recovery of the affected shoulder joint ROM, alleviate physical symptoms, and improve psychological adjustment and the QoL for early breast cancer patients. Hartman et al, 2007 Germany CCT N = 197; Treatment group = 98, control group = 99 Inclusion: Histologically confirmed BC <5 yrs; age 25 – 75; speaks sufficient German. Exclusion: Psychiatric disease; life expectancy <1 year; history of another cancer within last 5 years; inpatient treatment or breast recondition during study; lack of compliance. Treatment group - 3 week step-by-step inpatient and outpatient MD rehabilitation programme (physician input, psychology, physiotherapy), plus at 4 & 8 months later – a one week rehabilitation programme each time Control group - only one 4 week step-by-step inpatient and outpatient MD rehabilitation programme EORTC-QLQ-C30 Pre-intervention (baseline), end of 3 or 4 week programme, 12 months • Compared with the control group, the treatment group showed a improvement in gQoL, emotional function and cognitive function after 4 weeks, however, this was not statistically significant (gQoL 16 vs 12.6 p = 0.098, EF 30.7 vs. 23.7 p = 0.066, CF 11 vs. 4.5 p = 0.13). • Mean changes of physical function were similar in both groups (4.5  vs. 4.2,  p=0.7). • At 12-month follow up intervention group improved their  cognitive function by 2.3 whereas it decreased in control group by -5.5 this difference between groups became significant (p=0.0098). • Changes of other dimensions of QoL showed no difference   Step by Step rehabilitation programme was shown to be superior to the conventional rehabilitation programme with regard to the QoL.  Gordon et al, 2005 Australia Prospective cohort study n=275 Intervention = 67 (group 1 = 36, group 2 = 31), control = 208 Inclusion: confirm diagnosis with primary BC, with unilateral disease, able to speak English, with no cognitive problems; aged 25–74 years. Exclusion: very ill, if previously attended one of the two interventions Treatment groups: two outpatient low-technology, rehabilitation programmes with common and key goal of restoration of upper-body strength and flexibility and general support– early home-based physiotherapy intervention (Domiciliary Allied Health and Acute Care Rehabilitation Team ‘DAART’) or a group-based exercise and psychosocial intervention (Strength Through Recreation Exercise Togetherness Care Health ‘STRETCH’) programmes Control: women with BC from another project, with no intervention. FACT-B, DASH   Pre-intervention (baseline), post-intervention, 6- and 12-months from the date of diagnosis • Comparing pre/post-intervention measures, benefits were evident for functional well-being, including reductions in arm morbidity and upper-body disability for participants completing the DAART service at 1-2 months. In contrast, minimal changes were for the STRETCH group at approximately 4-months post-diagnosis. • Overall, mean HRQoL scores improved across all groups from 6- to 12-months and no differences were found, however, this obscured declining HRQoL scores for 20–40% of women at 12 months post-diagnosis, despite receiving supportive care services. • Social and emotional well-being scores showed no statistical significant differences over time 6–12 months post-diagnosis (p = 0.88 and p = 0.41, respectively). • Sub-group analyses of proportions of women with declined, unchanged or improved HRQoL scores; at 12-months post-diagnosis, participants in the unchanged group had high scores, which were very similar to scores of participants in the improved group and substantially higher than those participants in the declined group; all were statistically significantly different ( p < 0.05 ), except for DAART women for FACT-G, FACT-B & DASH scores Professionally led group exercise therapy with psychosocial care appears to have a neutral effect on upper-body recovery and improving HRQoL. However, it provides advantages for attendees in the form of peer-support, education, a holistic focus and the potential for addressing previously unrecognised psychological problems in a caring and acceptable environment. Koinberg et al, 2006 Sweden Prospective cohort study N = 96 Intervention = 50, control = 46 (1 loss to follow-up) Inclusion: BC classified as stage I or II, ability to speak Swedish and psychologically capable of participating Exclusion: not provided Treatment group: outpatient MD educational programme led by a specialist nurse, with PT, SW, a physician and BC patients’ advocacy group member, 4 sessions for 4 weeks, 2 – 6 months post surgery Control: traditional follow-up to a physician programme (2 times a year) FACT-G, SCA, SOC At diagnosis (1 month following surgery-pre-intervention) and 12-months • The women in the MD educational programme increased their physical and functional well-being (P<0:01). • No differences either between groups or within groups with regard to coping ability, participation in decision-making and knowledge about the disease at baseline or the 1-year follow-up • The women in traditional follow-up by a physician increased their functional well-being while social/family well-being (P<0:01) decreased over time. • Women in the traditional follow-up by a physician scored statistically significant lower in the area of sense of coherence in 1 year (mean = 74.4, SD = 12.4 and mean = 67.7, SD = 11.4, for baseline and 1-year follow up, respectively; P<0:001).   A MD educational programme may be an alternative to traditional follow-up by a physician after breast cancer surgery, but more research is needed about the financial benefits and effectiveness of such a programme. Strauss-Blasche et al 2005 Austria Pre-post design N = 149 (33 patients drop out) Inclusion: all patients who had had BC surgery within the last 72 months Exclusion: not specified. Treatment group: inpatient MD rehabilitation programme incorporating manual lymph drainage, exercise therapy, massage, psychological counselling, relaxation training, balenotherapy (carbon dioxide baths, and mud packs) Control:  for Mud packs therapy only N= 25, No mud packs N = 50 (matched control) EORTC QLQC30, HADS, serological marker CA 15-3, GICQ Pre-intervention (2 weeks before), at the end of the programme (3 weeks), and 6 months post programme • QoL, including function, physical complaints, and mental wellbeing, improved significantly from 2-weeks before rehabilitation to the end of rehabilitation (mean ES =0.49). The greatest short-term improvements found for mood-related aspects of QoL. • Mean ES for to 6 months follow-up=0.31, the largest sustained improvement found for social functioning, pain and fatigue, followed by emotional functioning and depression. • Older patients, non-obese patients, patients with a greater lymphoedema and patients with an active coping style showed slightly greater improvements. • The tumour marker CA 15-3 declined significantly to follow-up in those receiving mud packs. Inpatient rehabilitation, in combination with spa therapy, can be seen as a promising measure for improving QoL in BC patients. Pinto e Silva et al 2008 Brazil Prospective cohort study N = 89 (9 patients drop out) Intervention groups = 61: 2 groups (sentinel node biopsy (SNB) = 30; complete axillary lymph node dissection (ALND) = 31. Control group = 28 randomly allocated from SNB group. Inclusion: women treated for stages I and early II BC, undergoing quadrantectomy or simple mastectomy without distant metastases and prior malignancy Exclusion: not specified. Treatment group: inpatient postoperative MD rehabilitation programme provided by PT, SW, nurses & psychologists. Control: (only the SNB group) clinical follow-up FACT-G, FACT-B, TOI, EWB, BCS Pre-intervention (baseline), at the end of the programme 30 days postoperative, and 6 months • Women undergoing ALND had a better QoL within 30 days of surgery on the FACT-B (P = .0117), FACT-G (P = .0425), TOI (P = .0104), EWB (P = .0003), and BCS (P = .001). • Improvement remained significant 6 months after surgery only on the EWB subscale (P = .0204). • Women undergoing SNB had a better QoL only on the EWB subscale, which was significant 6 months after surgery in the group with rehabilitation (p = .03) and 30 days after surgery in the group without rehabilitation (p = .04) • Chemotherapy did not interfere with QoL in all groups. Comparing the mean FACT-B and its diverse subscales among the different groups at the three time periods evaluated, there was no difference in QoL among the groups at any time period studied. • EWB subscale improved significantly (P = .0041) for all groups with time. Women undergoing ALND benefited from a rehabilitation programme and had a better QoL. Women undergoing SNB, regardless of rehabilitation, showed improvement in QoL for the emotional well-being subscale only. BC = breast cancer, BCS = Breast Concern Subscale, CARES-SF = Cancer Rehabilitation and Evaluation System - short form, DASH = Disabilities of the Arm, Shoulder and Hand, DASS = Depression, Anxiety and Stress Scale, EORTC QLQC30 = European Organisation for Research and Treatment of Cancer (EORTC) for QoL Questionaries, EWB = emotional well-being, FACT-B = Functional Assessment of Cancer Therapy – Breast Cancer, FACT-G = Functional Assessment of Cancer Therapy-General, GICQ = German illness coping questionnaire, HADS = Hospital Anxiety and Depression Scale, N = total number, OT = Occupational therapists, PT = physiotherapist, PIPP = Perceived Impact of Problem Profile; QoL= quality of life, , SCA = Self-Care Aspects questionnaire, SOC = Sense of Coherence scale, , SW = social worker, TOI = Trial Outcome Index, ROM = Range of motion

Table 1: Summary of included studies.