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Methods to improve rehabilitation of patients following breast cancer surgery: a review of systematic reviews

Context Breast cancer is the most prevalent cancer amongst women but it has the highest survival rates amongst all cancer. Rehabilitation therapy of post-treatment effects from cancer and its treatment is needed to improve functioning and quality of life. This review investigated the range of methods for improving physical, psychosocial, occupational, and social wellbeing in women with breast cancer after receiving breast cancer surgery. Method A search for articles published in English between the years 2009 and 2014 was carried out using The Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, PubMed, and ScienceDirect. Search terms included: ‘breast cancer’, ‘breast carcinoma’, ‘surgery’, ‘mastectomy’, ‘lumpectomy’, ‘breast conservation’, ‘axillary lymph node dissection’, ‘rehabilitation’, ‘therapy’, ‘physiotherapy’, ‘occupational therapy’, ‘psychological’, ‘psychosocial’, ‘psychotherapy’, ‘exercise’, ‘physical activity’, ‘cognitive’, ‘occupational’, ‘alternative’, ‘complementary’, and ‘systematic review’. Study selection Systematic reviews on the effectiveness of rehabilitation methods in improving post-operative physical, and psychological outcomes for breast cancer were selected. Sixteen articles met all the eligibility criteria and were included in the review. Data extraction Included review year, study aim, total number of participants included, and results. Data synthesis Evidence for exercise rehabilitation is predominantly in the improvement of shoulder mobility and limb strength. Inconclusive results exist for a range of rehabilitation methods (physical, psycho-education, nutritional, alternative-complementary methods) for addressing the domains of psychosocial, cognitive, and occupational outcomes. Conclusion There is good evidence for narrowly-focused exercise rehabilitation in improving physical outcome particularly for shoulder mobility and lymphedema. There were inconclusive results for methods to improve psychosocial, cognitive, and occupational outcomes. There were no reviews on broader performance areas and lifestyle factors to enable effective living after treatment. The review suggests that comprehensiveness and effectiveness of post-operative breast cancer rehabilitation should consider patients’ self-management approaches towards lifestyle redesign, and incorporate health promotion aspects, in light of the fact that breast cancer is now taking the form of a chronic illness with longer survivorship years.


Introduction
Breast cancer incidences ranges from 19.3 per 100,000 women in Eastern Africa to 89.7 per 100,000 women in Western Europe and about 40 per 100,000 in developing countries. 1 The 5-year relative survival rates for breast cancer in the US have improved dramatically from 63% in the 1960s to 90% in 2011. 2 In Malaysia, the survival rates estimated in 2009 was 43.5%, with Malay, Chinese, and Indians, and Malays having 5-year survival rates of 39.7%, 48.2%, and 47.2% respectively, and the rates have also improved annually. The number of breast cancer survivors has increased dramatically as a result of early detection, better treatment, and various multidisciplinary rehabilitation methods. 3,4 However, improved survival rate of breast cancers also comes with numerous side effects from the cancer and its treatment. There is a need for comprehensive rehabilitation methods to address the many impacts of the long-term effects of this treatment, including the less recognized cognitive impairments 5 to improve survivors' global functioning.
Surgery is usually conducted with the goal to completely remove breast tumors, either by mastectomy or lumpectomy, and to assess the status of the axillary lymph node, either through sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). 6,7 Often, post-surgery rehabilitation focuses on the more obvious side effects, with pain and physical impairments being reported as the most debilitating complications after surgery. Therefore, commonly reported are upper body symptoms such as shoulder functions, breast/arm swelling (or lymphedema) with deformity, impairment of functionality, physical discomfort and numbness of the skin on upper arm and impaired arm. [8][9][10] Reports from lymphedema studies showed it occurs in 10%-50% of women who underwent ALND and among 5%-20% of women who underwent SLNB. 11 Post-operative, long-term pain has also been reported in 12%-50% of women with breast cancer, usually due to nerve injuries during surgery. 12 Prevalence of cognitive impairment occurs in 10%-50% of women. 7,13 It impacts on daily living performances (activities of daily living, work, and leisure tasks) and the overall quality of life (QoL), but is often ignored, partly because its cause cannot be identified. Furthermore, occupational outcomes, such as time needed to return to work, work absenteeism, and sick leave or employment status is also a concern of breast cancer survivors. [14][15][16] Emotional distress caused by shifts in social support, and fear of recurrence and death has also impacted women's wellbeing. 17,18 However, the rehabilitation is less commonly reported and includes the less obvious psychosocial functioning, including anxiety and depression, and where esthetic deformity or affected body image have been implicated leading to poor coping strategies. 19 As such, these after-effects from the post-operative procedures and adjuvant therapies can lead to a compromised QoL. 20 Holistic rehabilitation including health-promotion and health-prevention strategies, and via early Occupational therapy involvements is warranted for effective living with breast cancer.

Description of intervention
Management of long-term side effects of breast cancer treatment is important to improve QoL of breast cancer survivors. 21 Optimal rehabilitation includes the inputs from the various health professionals to help remediate and restore the impaired physical, psycho-social, and occupational functioning of women with breast cancer. 22 Some of these methods include physical-therapy, 23,24 exercise interventions, 25,26 psychological therapies such as psycho-education, 27,28 occupational therapy, 29,30 nutritional rehabilitation, 31 alternative rehabilitation such as yoga, music therapy, 32,33 and complex rehabilitation. 34

Aim
This review aims to examine systematic reviews on the rehabilitation methods for post-operative women with breast cancer, with a view on the comprehensiveness of these methods used, and if they consider breast cancer as a chronic illness. The findings may help inform suitable treatment decisions towards post-operative complications and the after-effects so that survivors can live for indefinite periods, with breast cancer taking a form of chronic illness.

Search terms
Systematic reviews were searched in four databases, restricted to full-text English language publications, which were published between January 2009 and October 2014, on adult women with breast cancer including The Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, PubMed, and ScienceDirect.

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Methods to improve rehabilitation of patients filter " asterisks (*)" were used together with the search terms to ensure all keyword variations were searched. Grey literature was excluded.

Selection of reviews
The electronic searches resulted in a number of studies uncovered from each database and was recorded immediately as shown in Figure 1. The online reference manager (EndNote) was used to remove any duplicates. Reviews were reviewed by one reviewer (ANM) to first assess their eligibility by reading the title and the abstract of each study.

Participants
Systematic reviews which include a sample of post-surgery breast cancer adults (aged 18 years and over) were included. Reviews were excluded if the sample had other types of non-breast cancer.
intervention Systematic reviews on the effectiveness of single/combined (complex) rehabilitation eg, physical/occupational therapy, exercise, psychological, occupational, cognitive, nutrition, and alternative methods for post-operative breast cancer. The interventions included: • Physical therapy -complex decongestive therapy, manual lymph drainage (MLD), standard physiotherapy, occupational therapy etc. • Physical exercise -home based and instructed exercise.
• Complex -combined interventions eg, counseling and exercise.

Types of studies
All published systematic reviews in the English language, on rehabilitation programs (for a combination of dysfunctions) were selected. The programs could have been physical or exercise or psychological or cognitive or occupational or nutritional or alternative or complex rehabilitation. There were no restrictions on the type of systematic

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Loh and Musa review, ie, systematic reviews of randomized controlled trials (RCTs), uncontrolled trials, non-randomized studies, qualitative, etc, provided that the aim of the study was to investigate the effects of either single or combinational rehabilitation methods/programs for post-operative patients with breast cancer. Systematic reviews were excluded if they focused on one narrow aspect or just one modality (eg, just specifically arm lymphedema as the outcome) and/or if there is less than four studies in the review paper, or it utilized less than three databases to search for individual studies.

Outcome measures
Systematic reviews on the physical, cognitive, occupational, and psychological outcomes in post-operative breast cancer patients were included: • Physical outcomes -shoulder mobility, lymphedema, wound healing, fatigue, etc.

eligibility criteria
The present systematic review included published systematic review articles in the English language between the years 2009 and 2014. Unpublished reviews (grey literatures) were not included in the review. Inclusion criteria were kept relatively broad to ensure comprehensiveness in assessing the various rehabilitation methods reviewed in previous systematic reviews.  Reviews were selected based on inclusion and exclusion criteria as depicted in the flow diagram ( Figure 1). All relevant reviews accessed were followed-up to establish inclusion. The information extracted included data from the data extraction table (Table S1) guided by a previous systematic review of reviews. 35 The data were extracted by one researcher (ANM) which was guided, assessed, and reviewed by a senior researcher (SYL). It was expected that there would be heterogeneity in the outcomes measured.

Risk of bias in individual studies
Methodological quality of included systematic reviews was independently rated according to the "assessment of multiple systematic reviews" (AMSTAR) tool. 36 Responses of the AMSTAR tool are 'yes', 'no', 'can't answer', or 'not applicable', with yes being rated as '1', and 'no', 'can't answer', or 'not applicable' rated as '0'. Based on this scale, reviews were rated as 'low', 'moderate' or 'high' quality. The domains identified in the 11-item tool are presented in Table 2. Figure 1 is the flow chart of the systematic review process from four databases (Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, PubMed, and ScienceDirect), which yielded seven full-text systematic reviews, 7,22,37-41 and excluded eight full-text reviews. 8,[42][43][44][45][46][47][48] Reasons for the exclusion of reviews are stated in the screening inclusion and exclusion table (Table S1). Table 3 shows the AMSTAR tool for assessing methodological quality or rigor of each review included. Based on the AMSTAR tool, three out of the seven reviews reported were of good methodological quality, 22,37,38 with three RCTs of medium quality, 7,39,40 and one review of low quality. 41 All but one systematic review 41 had ensured at least two independent researchers had been involved in data extraction, or at least one researcher had checked the other's work. All, but one review 7 had ensured a comprehensive literature search (ie, a search strategy using more than two databases and one supplementary strategy that uses review of references in individual studies). Only one systematic review 38 had searched for and attained unpublished or grey literature. Three reviews 22,37,38 had ensured a list of included and excluded studies, with reasons for inclusion and exclusion provided. Methodological quality assessments of included studies were measured in all, but one review. 41 However, only two reviews 38,40 had considered the methodological quality of each individual study in carrying out a conclusion or recommendation of rehabilitation methods. All, but two reviews 7,41 had assessed heterogeneity of included studies reviewed. Publication bias was assessed. In two reviews 38,39 publication bias could not be assessed since the number of included studies was less than 20.

Characteristics of included reviews
A summary of the review is presented in Table 4, outlining its year of publication, aim, search strategy used, inclusion and exclusion criteria, number and design of included studies in each review, total number and age of participants, and outcomes measured.

Description of methods
The selected systematic reviews vary considerably in terms of the designs of the studies included, type of rehabilitation methods, and search strategy (databases used, publication years and language restriction, and search terms) (Table S2). Five out of the seven systematic reviews were RCTs. 22,[37][38][39][40] One review included both controlled and uncontrolled quantitative trials. 41 Another study included qualitative studies only. 7 Three reviews had specifically investigated physical rehabilitation methods: two papers were on the efficacy of various types of exercise, 37,38 whilst one was on weight training exercises. 39 One review investigated psychosocial interventions, 40 another the efficacy of occupational rehabilitation on women with breast cancer, 41 and one explored cognitive functioning. 7 Only the review by Juvet et al 22    1. was an "a priori" design provided?

covered a holistic range of rehabilitation
Yes was there duplicate study selection and data extraction? Yes was the status of publication (ie, grey literature) used as an inclusion criterion? Yes was a list of studies (included and excluded) provided? Yes were the characteristics of the included studies provided? Yes Was the scientific quality of the included studies assessed and documented? Yes Was the scientific quality of the included studies used appropriately in formulating conclusions? Yes Were the methods used to combine the findings of studies appropriate? Yes . was the likelihood of publication bias assessed? Yes

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Methods to improve rehabilitation of patients methods -physical activity rehabilitation, psychosocial rehabilitation, nutritional rehabilitation, complementary or alternative rehabilitation (ie, yoga, music therapy, etc), and complex (psycho-education plus counseling) rehabilitation for women after breast cancer. 22 For each of the resulted review, we had searched in more than one database for individual studies (refer to Table 4). Restriction of publication years and language varied across the seven reviews. Chan et al 37

Description of participants
The total number of participants was specified in all seven reviews. The age of participants was specified in three reviews [37][38][39] only. Details of the total number and age of participants are provided in Table 4. All but three reviews 38,39,41 specified exclusion criteria for participants. Chan et al 37 excluded reviews which included male participants.

Description of outcomes
Physical, psychosocial, occupational, and cognitive outcomes varied. Amongst the physical outcomes assessed were: upper body symptoms (ie, shoulder function, arm movement, limb strength), 37,38 risk or incidence of secondary lymphedema, 37-39 fatigue, 40 pain, 38 seroma formation, 38 wound drainage, 38 physical fitness (ie, body mass index [BMI], body composition), 22,39 and adherence to exercise. 38 Amongst the psychosocial outcomes were QoL, 38-40 mood, health behavior, and social function. 40 Occupational outcomes included return to work, absenteeism, work disability, sick leave or employment status measured by only one systematic review. 41 Cognitive outcomes include perception of "chemo-brain", coping strategies towards cognitive dysfunction, and self-management as breast cancer survivor. Only one review 22 had attempted to look at somatic, psychological, and social outcomes as a comprehensive whole. Table 5 shows the results of the effects of various rehabilitation methods on physical outcomes. Five reviews had investigated the effects of rehabilitation for physical outcomes, with adequate methodological quality: three reviews were rated as having high methodological quality, 22,37,38 and two were rated as having medium quality. 39,40 Exercise rehabilitation showed significant improvement in shoulder movement -irrespective of type or time period of implementation 37 but, early exercise was found to be more effective than delayed exercise. 38 Paramanandam and Roberts 39 found that gradual intensity weight training, with slow progression, improved upper and lower limb strength. More importantly, exercise did not increase risk or change in the incidence rate of lymphedema 22,37-39 and complex decongestive therapy decreased the incidence of lymphedema as compared to standard physiotherapy. 22 The benefits of exercise were well reported. Early exercise (versus delayed) also helps wound healing by increasing the wound drainage volume. 38 There were inconclusive results for exercise interventions on BMI. 22,39 With fatigue management, psycho-education had a significant short-term benefit, 40 but not cognitive behavioral therapy. 22,40 With hot flashes, complementary rehabilitation (acupuncture, yoga, art therapy, or relaxation training) did not show conclusive evidence. 22 Overall, the physical rehabilitation seems to focus on shoulder range of motion, fatigue, body weight, wound, and hot flashes amongst the wide range of after-effects from breast cancer and its treatment. effects on non-physical related outcomes Table 6 shows the effects of rehabilitation methods on less obvious psychological, occupational, and cognitive outcomes. Of the five reviews, the methodological quality of the three reviews was rated as high quality, 22,37,38 and two reviews 39,40 were rated as medium quality.

Findings effects on physical outcomes
QoL was assessed in three reviews 22,39,40 as an outcome of exercise rehabilitation, 22,39 CBT, 40 and psycho-education 22,40 albeit with inconclusive results. One review 22 found inconclusive results on the benefit of both complementary and complex decongestive therapy on QoL. Health behaviors and social function and coping were assessed in two reviews 22,40 with inconclusive results. There were inconclusive results of social and emotional support interventions in two reviews. 22,40 Mood outcomes such as anxiety, event related distress, and depression assessed in two reviews 22,40 found that psychoeducation, CBT, and social and emotional support interventions yield inconclusive results towards improving mood. There was some evidence that complementary intervention  Table 5 Results of studies on rehabilitation methods on physical outcomes  was addressed in two studies, relaxation training intervention reduced the incidence, while acupuncture also reduced but did not reach statistical significance Abbreviations: ALND, axillary lymph node dissection; BCT, breast conservative therapy; BMI, body mass index; CBT, cognitive behavior therapy; MRM, modified radical mastectomy; MLD, manual lymph drainage; RCTs, randomized controlled trials; ROM, range of motion; SLNB, sentinel lymph node biopsy.
after primary breast cancer treatment was found to have a small effect on mood outcomes. 22

Rehabilitation methods for cognitive outcomes
Cognitive outcomes were measured in one review only. 7 Psychosocial interventions and practical reminders were adequate coping strategies towards cognitive dysfunction but the meta-ethnography review also found cultural differences in coping strategies, such as Asian women being more likely to use complementary medicine like medicinal herbs, to improve cognitive functioning.

Rehabilitation methods on occupational outcomes
There were inconclusive outcomes with occupational rehabilitation 41 -whether rehabilitation consisting of counseling or exercise would indeed decrease time needed to return to work in breast cancer survivors. However, the review showed that the extensiveness of the surgical procedures correlates with the length of time needed to return to work.

An over-emphasis on physical dysfunction
Effectiveness of rehabilitation methods on physical, psychosocial, cognitive, and occupational outcomes vary according to numerous type/s of rehabilitation methods used. Reviews investigating physical outcomes dominate the literatures. There were relatively less systematic reviews on cognitive outcomes and occupational outcomes, both were reviewed by Selamat et al 7 and Hoving et al 41 respectively and both suggests a lack of work and acknowledgment by health professionals and survivors in this area of cognitive impairment. Exercise was found to be effective in improving shoulder mobility, limb strength, and wound healing, although it was found to be inconclusive for fatigue and body composition (ie, BMI) management, and lymphedema. In fact with the common fatigue post operation, more work is needed as there were inconclusive findings for psycho-education, CBT, and social-emotional rehabilitation for fatigue management. There were also inconclusive results for the efficacy of complementary rehabilitation (acupuncture, yoga, art therapy, or relaxation training) on hot flashes. Overall, exercise seems to be the one rehabilitation method to improve the narrow physical outcomes eg, for shoulder mobility, and irrespective of the type of exercise implemented. The benefit of broader exercise such as exercise for lifestyle redesign for a preventive stance  Table 6 Results of studies on rehabilitation methods on psychosocial, occupational, and cognitive outcomes

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Methods to improve rehabilitation of patients against cancer recurrence and for better QoL, needs more research. There are some studies, both quantitative and qualitative 49,50 which have highlighted barriers to exercise 5 years after diagnosis of breast cancer and uncovered many expressed psychological barriers (eg, low motivation, dislike of gym), environmental barriers (eg, employment-priority, low access to facilities, interfering seasonal weather, traffic congestion to get to the gym), and lack of time. As such, studies are also needed on interventions to overcome these barriers to exercise and to ensure adherence to exercise regimes to gain its benefit on cancer recurrences and for better quality of living during the survivorship phases.
A lack of evidence for non-physical rehabilitation methods Reviews showed inconclusive results were found for the efficacy of rehabilitation methods using psycho-education, CBT, social-emotional support, complementary-alternative methods towards improving health behaviors and/or QoL. In general, the review of the reviews also found inconclusive results on social functioning, coping, and mood outcomes. However, complementary intervention may have a small effect on mood outcomes. Nevertheless, the studies are largely heterogeneous in terms of type, length, and components of rehabilitation methods which make the comparisons rather difficult to carry out.
For less recognized problems faced by survivors of breast cancer, qualitative research identified "chemo-brain", and attitudinal changes towards work. 7,51 Psycho-social rehabilitation and practical reminders were strategies proposed to improve cognitive function despite variations due to cultural differences. With occupational rehabilitation, inconclusive results were found on whether exercise or counseling rehabilitation would decrease time needed to return to work in women with breast cancer. 41 Qualitative findings from focus groups of multi-ethnic survivors have highlighted several barriers such as fear of environmental hazards, high jobdemand, intrusive thoughts and family over-protectiveness, 30 as well as other socio-demographic factors eg, education, range of treatment received, strenuous physical work, fatigue, and psychological factors such as negative mood. 52 Future occupational studies should investigate the breadth and depth of rehabilitation methods (eg, work stamina, tolerance, psychological factors for facilitating work re-entry, work accommodations such as flexibility towards work hours etc) for enabling post-operation survivors to return to work in a design that has a control or comparison group (ie, other types of interventions, wait-list, etc).
A need for more comprehensive methods to enable living for indefinite period Overall, the lack of evidence for non-physical rehabilitation methods highlight the lack of research work that extend beyond the rehabilitation methods for physical after-effects. The gradual acknowledgment that breast cancer is taking a form of chronic illness 53 is not proportionate to the current rehabilitation methods which suggest an overall management of breast cancer as an acute/fatal condition. Amongst the important implications of this current review is that rehabilitation for women with breast cancer should be comprehensive (ie, broader rather than eg, narrowly focused on upper limb function) and proactive (rather than reactive). This stance is a better preparation of breast cancer survivors to live indefinitely with the condition and to empower them to re-engage in lifestyle modification and/ or lifestyle redesign, 54 in order to address ill-health, and improve their wellbeing, lifespan, and QoL. The specific, but predominantly performance component rehabilitation, such as improving shoulder mobility, is effective but not sufficient to enable or inform survivors to live the best they can for the remainder of their life span. The lack of emphasis on patient self-management and occupational redesign towards a healthier lifestyle suggests a dire lack of focus on these broader aspects of life. This also showed a lack of appreciation that breast cancer is evolving into a form of chronic disease requiring a brand new platform to support its increasing numbers of survivors.

Limitations
The main limitation of this systematic review on systematic reviews is the difficulty to synthesize because of the heterogeneous nature of the methodology of each review. There were varying inclusion-exclusion criteria, different outcome measures, which leads to difficulties extracting and synthesizing the data.

Conclusion
In conclusion, the current rehabilitation methods tend to focus narrowly on performance components (particularly on physical impairments or dysfunctions). The review found evidence that exercise rehabilitation methods improves physical outcome post operation, although, inconclusive results exist on rehabilitation methods to improve the non-physical sequelae such as psychosocial, cognitive, occupational, and broader lifestyle performance factors. Clearly missing are the rehabilitation methods to enable survivors to redesign their lifestyle in tandem with living with a breast cancer

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Loh and Musa condition that is taking a form of chronic disease. This calls for health prevention and illness prevention lifestyle strategies to i) control cancer recurrence and ii) to promote better QoL during the indefinite period of survivorship. With the overwhelming strong evidence that cancer risk is affected by lifestyle, future studies with higher methodological rigor should be conducted on health promotion strategies to enable healthy lifestyle.

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