Journal of Oncology Research and Therapy (ISSN: 2574-710X)

Article / research article

"The Effects of Supervised Exercises Program on upper limb dysfunction and Quality of Life in breast cancer survivors following different treatment strategies: Meta-Analysis"

Jean Paul Muambangu Milambo1*, Leonidas Ndayisaba2, Landry Kabego3, Kazadi Vallery Tshilombo4, Jacques Lukenze Tamuzi5
1Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University and NHLS, South Africa
2Department of Respiratory Intensive Care, Groote Schuur Hospital, Cape Town, South Africa
3Bukavu General Hospital/Université Catholique de Bukavu, Department of Pathology, Democratic Republic of the Congo
4,5Division of Health Systems and Public Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
 
*Corresponding author: Jean Paul Muambangu Milambo, Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University and NHLS; Cape Town, 25 Norden Road, Parow 7500, South Africa. Tel: +27719953868; Email: drjpmilambo@gmail.comJeanpaulmilambo2@gmail.com 
Received Date: 12 February, 2018; Accepted Date: 20 August, 2018; Published Date: 28 August, 2018

1.       Abstract 
1.1.  Purpose: The review was conducted to assess the efficacy of supervised exercises program in reducing upper limb dysfunction and improving health related quality of life among breast cancer patients following different treatment strategies.   
1.2.  Methods: PRISMA was used to conduct the present review of literature in PubMed/Medline, Embase and Cochrane Breast cancer registry. The study included only randomised controlled trials investigating the efficacy of medically supervised exercises program versus no supervised exercises programs. The details of exercises mode, frequency, length of follow up and BCRL mean reduction and HRQOL scores were computed for meta-analysis. The guideline for exercises regimen published by ISL and American College of Sports Medicine exercise guidelines for cancer survivors were included in the present study just limited to English language. Two authors performed data extraction, eligibility criteria and risk of bias assessment independently and the third reviewer was consulted for disagreement.
1.3.  Results: Meta-analysis was performed using a random-effects model for potential nine RCTs. The results have illustrated the MD of BCRL volume reduction (%) between supervised versus no supervised exercises was 1.35 (95%CI 0.63 to 2.07, 6 studies, 371 females, P=0002). Heterogeneity: Tau² = 0.71; Chi² = 112.14, df = 5 (P < 0.00001); I² = 96%. These results have shown that the MD was 35% reduced in supervised exercises compared to no supervised exercises (Statistically significant with P=0.0002) Forest plot Figure 2. However, the statistical heterogeneity between RCTs was high. The pooled summary of supervised exercises versus no supervised exercises in improving HRQOL has shown that supervised exercises enhanced the MD HRQOL compared to no supervised exercises 3.02 (95%CI 2.59 to 3.45, 4 studies, 201 females, P <0.00001). The results were statistically significant.
1.4.  Conclusion: The findings from our meta-analysis revealed that supervised medically exercises combined with CDT are more effective in reducing LE volume and potentially improve HRQOL among BCRL survivors. The studies on the effect of the supervised exercises on LE survivor’s adherence and the exercises mode and frequency are recommended to extend the level of evidence. The healthcare providers should consider ISL guideline for supervised exercise prescription in clinical settings. 
2.       Abbreviations 
ACS        :               American Cancer Society
ACSM    :               American College of Sports Medicine
BIS         :               Bioimpedance Spectrometry
BCRL    :               Breast Cancer-Related Lymphoedema
BMI       :               Body Mass Index
BC          :               Breast Cancer
CDT       :               Complex Decongestive Therapy
HRQOL :               Health Related Quality of Life
ISL         :               International Society of Lymphedema
LE           :               Lymphedema
LCM      :               Limb Circumference Measurement
MLD      :               Manual Lymphatic Drainage
MSEP     :               Medically Supervised Exercise Program
QOL       :               Quality of Life
ROM      :               Range of Motility
RCT       :               Randomized Controlled Trial
SF           :               Short -Form
SLE        :               Secondary Lymphedema
ULL27   :               Upper Limb Lymphedema 27
USA        :               United States of America
VAS        :               Visual Analogue Score 

3.       Introduction
Breast Cancer-Related Lymphedema (BCRL) is known long-life complication related to breast cancer management [1-5]. It is resulted to lymphatic system dysfunction which affects the function, psychosocial and economic implications of BCRL survivors [1-3,5-11]. The incidence of BCRL varies from 7% up to 83%; depending to various methods used to diagnose BCRL [5,12-14]. These include limbs circumference measurements, water displacement, patients self-reporting, laser scanning, Bio Impedance Spectroscopy (BIS) and optoelectricperometry [5,15-19]. These diversities methods used to define LE; have led to both over/under estimations of LE burden in literature [5]. The BCRL is a chronic inflammatory disease mainly associated with clinical management of breast cancer [11,20,21]. Its risk factors including surgery, radiation therapy, chemotherapy, Body Mass Index (BMI) > 25/kg2, ethnicity, age, cellulitis, and genetic susceptibility are the additional predictors for LE development [13-22]. The current standard of care recommended by International Society for Lymphology (ISL) for BCRL management is Complex Congestive Therapy (CDT) and exercises [23]. CDT improves Health Related Quality of Life (HRQOL), reduces BCRL volume, and increases the intention to exercise. It is a safe treatment for patients with ongoing local/regional tumours [23]. CDT includes Manual Lymphatic Drainage (MLD), compression sleeves, congestive exercises, skin care, and patient oriented education [23-26]. The exercises for patients with upper limbs LE have been discussed to be both risk reduction and risk factors in literature [27-37]. These exercises aim to restore the affected limbs, chest, cervical and thoracic trunk range of motion (ROM) and improve strength among BC following surgery [38-40]. The recommended medically supervised exercises programs aim to restore ROM, increase muscles strength, to maximize limbs function and management of LE related inflammation [37]. In addition, exercises improve arterial blood flow from heart to peripheral tissues and it increases the lymphoangegenesis [37]. The current position statement for cancer rehabilitation including SLE and associated post-surgery disabilities risk reduction were recommended by American Cancer Society (ACS) [30]; American College of Sports Medicine (ACSM) [38], and lymphedema related studies that the aerobic exercises of 150 min/week of moderate-intensity or 75 min/week of vigorous-intensity activity, or an equivalent combination should be initiated for each patient [39-50]. Resistance exercises should be performed for muscle-strengthening activities of at least moderate intensity at least 2 days/week for each major muscle group. The flexibility of stretch major muscle groups and tendons on days other activities should be performed. The 1-repetition maximum (1-RM) is a standard practice for muscle strength measurement, method to assess patient comorbidities and maximizes benefits of the patients during the resistance exercises. Evidence suggests that 59-69% of 1-RM should be lifted to improve muscle strength. The range of exercises repetition varies 8-12 repetitions for initiation [51]. Moreover, a review on the effect of exercises among BC patients related postoperative impairments revealed that mean Assessing the Methodological Quality of Systematic Reviews (AMSTAR) score = 7.66/11 (±2.04) suggested moderate quality of evidence for the benefits of slight, moderate and rigorous exercises in improving HRQOL among cancer survivors following radiation therapy and surgery. The addition results of the review revealed that medically patient oriented exercises programs were more effective comparing to non-supervised exercises programs and serious side effects were minimized [50]. The meta-analysis comparing supervised exercises and non-supervised exercises among BCRL have not yet conducted to evaluate the effects of these types of exercises for both the patients at both intense and maintenance phase of CDT. Further, the review conducted on the efficacy of exercises for LE risk reduction revealed that all different types of exercises are effective for LE management, but the exercises should be performed under medical supervision to prevent additional complications [48]. The review also identified that the recommended physical activity by ISL which include resistance and aerobic, aquatic, yoga could be prescribed under medical supervised, but the level of evidence was low to moderate for the most randomized clinical trials included. Personalized exercises program was recommended for BCRL survivors with the purpose to restore range of motility, increase muscle strength, increase upper limbs strength and to mitigate inflammation [46]. Lifestyle strategies which is include eating healthy combined with exercises for weight lost was also proved effective among BCRL survivors in improving HRQOL [30,32]. Although exercises were recommended as adjunct to CDT; Therefore, the adherence on the patients at maintenance of therapy without medical supervision is associated with decreased HRQOL due to poor adherence of LE survivors [52-53]. Data on the safety, intensity and duration of the exercises toward different stage of ISL stages are scanty internationally. No review has not yet conducted to evaluate the efficacy of supervised exercises program versus no exercise program for evidence based clinical practice recommendation for BCRL survivors. Therefore, this systematic review and meta-analysis was conducted to compare the efficacy of personalized oriented exercises programs versus no supervised exercises programs on BCRL risk reduction and in improving HRQL. Data from this meta-analysis can be used to guide clinical decisions, and support the development of evidence-based guidelines for recommendation of specific exercise protocol among BCRL patients at both intensive and maintenance phase of CDT. 
4.       Review Question 
are supervised medical exercises programs effective in reducing lymphedema volume and improves quality of life among women with breast cancer related lymphedema at intensive or maintenance phase of CDT comparing to no supervised medical exercises program combined with CDT’’? 
5.       Methodology 
5.1.  Search Strategy and Selection Criteria 
This meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline [54]. We conducted the search strategy and the clinical trials conducted in all countries that have been published in peer-reviewed medical journals. We conducted a review of literature in PubMed/Medline, Embase and Cochrane Breast cancer registry. The study included only Randomised Controlled Trials (RCTs) investigating the efficacy of medically supervised exercises programs describing mode of exercises, frequency, length of follow up and BCRL mean reduction and HRQOL scores were computed for meta-analysis. The guideline for exercises regimen published by ISL and American College of Sports Medicine exercise guidelines for cancer survivors were included in the present study just limited to English language. We used the search term: (Breast cancer related lymphedema [MESH] OR BCRL [MESH]) AND (supervised exercise program OR mentored exercise program) AND (quality of life [tw] OR QOL [tw] OR reduction in volume [tw]). The protocol of the review was registered with PROSPERO 2017 CRD42017079864 Available from:
Eligibility criteria were established using the PICO (participants, interventions, comparator and outcomes) framework for this review.
·                     Participants: RCT studies involving patients diagnosed with BCRL; with well detailed supervised exercises programmes (frequency, duration, ROM, types of exercises) of the patients treated with BCRL following their BC cancer management comparing to no supervised exercises. Mean differences, tools used to diagnose LE, p-values and 95% confidence interval were compared between intervention and control groups of the included studies without years and settings restriction. The review was limited with the articles published in English, and randomised controlled trials comparing two groups of participants using exercises as adjunctive to CDT. 
·                     Interventions: Medical supervised exercises programs with a specified and described exercise mode, intensity, duration, ROM, length of follow-up and records of adverse events if available. CDT combined with other forms of the exercises recommended by ISL were also included. These comprised stretching exercises, aerobic exercises, weight lifting, resistance exercises, aqua exercises, swimming or walking. Other type’s patients-oriented exercises prescribed by healthcare providers were included if supervised by a sport physician or physiotherapist. In addition, trials reporting the female’s patients > 18 years old with BCRL (all clinical stages of LE were included). The types of the treatment used such as: surgical procedures performed for breast cancer with axillary lymph node dissection, sentinel lymph node biopsy or axillary sampling, with or without radiotherapy to the axilla or the supraclavicular fossa or both; or radiotherapy therapy combined with surgery or alone, chemotherapy combined with surgery or radiotherapy. 
·                     Comparators: Studies involving standard exercises for BCRL such as CDT related decongestive exercises, recommended resistance, aerobic exercises without medical supervision. Specified exercise regimen (frequency, duration, follow-up) and tools used to measure LE. 
·                     Outcomes: Studies involving lymphedema assessment using the recommended tools by ISL (limbs circumference measurements, BIS, water displacing, laboratory tests, lymphoscintigraphy, and self- reports). The validated QOL tools for upper limbs recommended by ISL were reported by the primary study’s authors. Additionally, level for physical function, symptoms related to comorbidity, psychosocial level, physical appearance, emotional status were assessed using the international classification of disability questionnaire. 
5.2.  Exclusion Criteria 
Children and adolescents, studies included men, BCRL women with metastatic cancer, pharmacological interventions, traditional medicines, Individual studies (non-randomized studies, case controls, duplicated studies, narrative reviews, no exercises defined interventions, studies included both primary and secondary LE, study without control groups, case studies, case reports, cross-sectionals, qualitative, systematic reviews and other languages than English. 
5.3.  Screening and Data Abstraction 
Two medical investigators (JPM, L) independently select the study abstracts, full articles and the risk of bias was performed using the tools. The senior researchers were consulted in case of risen disagreement (J.M, M.J.); and disagreements was resolved by commitment. The clinical heterogeneity was assessed by comparing the study designs, settings, sample sizes, countries of publication, methods used for diagnosis, identified risk factors and the outcomes measures at each study endpoint. Random effects meta-analysis was conducted for pooling of the effect size. Further, the statistical heterogeneity was evaluated by using chi-square test of homogeneity and I2 statistic test was conducted for quantitative data. The subgroup analysis was conducted for different tools used to measure the primary outcomes which is LE volume reduction and secondary outcomes included HRQOL standardized questionnaire for the identified a substantial heterogeneity. Articles were classified as potentially eligible if the titles indicated a Randomised Controlled Trial (RCT) on the prevention or management of BCRL. If no judgment could be made about the eligibility of a study based on the title, the judgment was based on title and abstract. Any disagreements about eligibility was resolved in consensus meetings. The same procedure was applied for references included in this systematic review. Review articles identified in the search were screened for relevance and reference lists were checked to identify additional potentially eligible studies. Final decisions about inclusion for all articles judged potentially eligible was based on the full text of the published articles. 
5.4.  Quality Assessment and Personal Study Quality 
Two authors (JPM, JL) independently assessed the quality of eligible nine RCTs (Table 1). Risk of bias was conducted using the Cochrane risk of bias tool for the appraisal of RCTs, as outlined in the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0 [55]. The tool contains six domains and each domain was assigned a judgement related to the risk of bias (Table 2 and Figure 5). The judgement could be ‘low risk’, ‘high risk’, or ‘unclear risk’. The latter judgement was assigned if the risk of bias of a characteristic in an included study was judged to be unclear, or if there was insufficient information on which to base the judgement. We compared excel datasets between two data extractors and the third author was consulted to resolve discrepancies. We reported the summary of the risk of bias in Table 2. All analyses were performed using Review Manager Software [55].
6.       Results 
Search strategy identified 4 408 reports. 4370 did not meet the eligibility criteria. A total of 38 articles were assessed. From these, 8 were wrong publications, 12 did not describe the exercises programs; 5 did not include well reported outcomes and 4 were duplicates. Nine eligible original RCTs with 483 patients met the inclusion criteria. No adverse events were reported in the included studies evaluating the efficacy of supervised exercises versus standard exercises among the patients treated for secondary LE. In addition, the resistance and aerobic exercises were common among the selected studies. The authors described the mode, frequency of each component of exercises regimen as recommend by ACS and ISL. 
6.1.  Exercises Mode, Frequency, Duration among Included Studies 
Buragadda, et al. [56] evaluated the efficacy of CDT and supervised community-based exercises on LE risk reduction and Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire was used to quantify HRQOL [57]. The exercises programs included glenohumeral mobilization, deep breathing exercises, and decongestive resistance exercises (5 days a week/ 6 weeks) and both groups used CDT as a standard of care. The tools used to measure the outcomes were respectively Limbs Circumference Measurement (LCM) and DASH questionnaire for HRQOL scores. The result of this study showed that supervised exercises programs at maintenance phase of CDT improved HRQOL and potentially decreased LE volume [56]. In addition, Milan, et al. [58] evaluated the supervised exercises combined with CDT on HRQOL using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) [59], and the authors found that supervised exercised coupled with CDT at maintenance phase improved QRQOL among BCRL survivors [58]. Hayes, et al. [60] assessed the effect of aerobic, resistance exercises and mixed (30- 5/ 3 times daily/12 weeks) coupled with CDT on LE reduction and QOL. The final result showed that Supervised exercises group improved in physical and psychosocial dimensions of HRQOL comparing to no supervised exercises group [60]. McClure, et al. [61] assessed the efficacy of supervised decongestive exercises on HRQOL, AROM; the maximum follow-up time was 17 weeks. The final report revealed that the supervised exercises increased adherence of BCRL patients on CDT and improved HRQOL comparing to no supervised exercises group [61]. Bushan, et al. [62] evaluated the efficacy of aerobic and resistance exercises (150 weekly, 3-5 times /12 weeks) on LE risk reduction, HRQOL and AROM, the tools used were BIS, self-report questionnaire for LE and DASH questionnaire. The result showed that there was no statistically significant difference between supervised exercises group comparing with no supervised exercises programs [62]. Kim, et al. [63] evaluated the effectiveness of resistance exercises (15 min/ daily, 5 days/ 8 weeks) on LE volume reduction and QOL; the tooled used were LCM and SF-36 scores. The results showed that supervised exercises group improved in HRQOL and LE reduction were significantly reduced comparing to no supervised group [63]. Schmitz, et al. [64] used water displacement to measure LE volume among two groups randomly allocated to supervised weight lifting exercises (90 min twice weekly/12 weeks fp). The results showed that progressive supervised weight lifting moderate to rigorous exercises reduced LE volume comparing to control group [64]. Irdelsel, et al. [65] evaluated the efficacy of aerobic and resistance exercises (3 to 6 months, 3 times daily) on LE risk reduction and AROM; the results showed that supervised exercises coupled with compression sleeves are effective than CDT coupled with non-supervised exercises. Sener, et al. [66] evaluated the efficacy of supervised pilates exercises (5- 8 persons 3 times weekly /8 weeks fp) on LE reduction and HRQOL; the tools used to measure outcomes were respectively LCM and DASH-30. The authors found that supervised clinical Pilate exercises are safe and could be considered for LE programs [66]. 
6.2.  Meta-Analysis and Heterogeneity Assessment 
Our screening revealed the studies of rigorous methods of RCTs. The six domains of risk bias assessed revealed that the biases were reduced in the most of included studies. 
This meta-analysis included nine RCTs, comparing the Mean Difference (MD) of age between Supervised and no supervised exercises in breast lymphedema cancer. The age range of the mothers varies from 50 to 60 years old. The MD of between supervised exercises and no supervised exercises was -0.34 (95%CI -1.23 to 0.56, 9 studies, 483 females) forest plot Figure 2. The results were not statistically significant with p-value of 0.46. The pooled effect size of supervised exercises versus no supervised exercises in reducing LE volume has shown low evidence that supervised exercises programs reduce LE volume compared to no supervised exercises 1.35 (95%CI 0.63 to 2.07, 6 studies, 371 females, P=0002). Heterogeneity: Tau² = 0.71; Chi² = 112.14, df = 5 (P < 0.00001); I² = 96%.
These results have shown that the MD was 35% reduced in supervised exercises compared to no supervised exercises (Statistically significant with P=0.0002) forest plot Figure 3. However, the statistical heterogeneity between RCTs was high. The pooled summary of supervised exercises versus no supervised exercises in improving HRQOL has shown moderate evidence that supervised exercises enhanced the MD HRQOL compared to no supervised exercises 3.02 (95%CI 2.59 to 3.45, 4 studies, 201 females, P <0.00001). The results were statistically significant. Forest plot Figure 4 shows the pooled effect size and grading is included in forest plot interpretation Figure 5. Heterogeneities were assessed in three forest plots. The overall clinical heterogeneity was high in all meta-analysis. Bias assessment revealed that the random allocation was adequate in all RCTs. Confounding was minimized and then the Cochrane tool of bias assessment does not mention it. Other risk of bias was likely; the final report was graded as moderate. Therefore, further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
6.3.  Meta-analysis
7.       Discussion 
This is the first meta-analysis conducted to assess the effect of personalized -patients oriented exercises programs in management of LE related breast cancer management as recommended by ISL. The findings from our meta-analysis revealed that supervised medically exercises combined with CDT are more effective in reducing LE volume (MD: 1.35 (95%CI 0.63 to 2.07, 6 studies, 371 females, P=0002). Heterogeneity: Tau² = 0.71; Chi² = 112.14, df = 5 (P < 0.00001); I² = 96%). The MD LE volume reduction was 35% in supervised exercises compared to no supervised exercises (P=0.0002). In addition, the pooled MD of HRQOL score of BCRL survivors in intervention group compared to control group was 3.02 (95%CI 2.59 to 3.45, 4 studies, 201 females, P <0.00001). The summary of findings has shown that supervised exercises programs are the best strategies to recommend in clinical practice for BCRL management as adjunct to CDT at both intensive and maintenance phase of CDT. Subgroups analysis for exercises mode (aerobic, stretching, weight lifting, mixed, yoga, swimming) were not conducted for heterogeneity of the regimen throughout the studies; the mean intervention duration was > 3 months < 6 months. The studies evaluating the effect of supervised exercises versus no supervised exercises on LE status were scarce in the included studies. Additionally, the studies evaluating the effect of medically supervised exercises on patient’s adherence on standard of care should give more evidence-based data to extend the body of the knowledge. Moreover, the mode of exercises and frequencies of exercises were not evaluated as prescribed by different protocols for exercises prescriptions as well as the exercises for each stage of LE based on ISL guideline still a challenge to be investigated in further studies. 
Considering the impact of LE for BCRL survivors with associated functional limitations, psychosocial distress, and economical implications of patients; the efforts need to be made to reduce his incidence which is globally health system challenge. Due to global high burden of breast cancer and the techniques used to manage this condition [67-75]. 
Currently, the evidence supports the use of CDT to improve HRQOL, reduce LE volume and increase patients’ ability to exercise [23]. CDT is considered the standard care for LE management, but the level of evidence is not yet established for each component of this intervention. Two reviews conducted on the conservative therapies of BCRL demonstrated that all types’ exercises and self-management may be effective to reduce LE and to improve HRQOL [10,23]. The evidence available on efficacy of CDT and the results of clinical trials are controversial and inconclusive for its recommendation at maintenance phase of therapy without adjunctive therapy. In addition, CDT alone were proved ineffective at maintenance phase of therapy and many countries faced the economic challenges to implement CDT as standard of care although it international accreditation [52,53]. Lifestyle strategies which include both eating balanced diet and physical activity were recommended based on evidenced based clinical trials [32,36]. For the above limitations related to CDT implementation and lack of high level of evidence for its efficacy at maintenance phase of BCRL survivors; the authors identified that patient’s non-adherence on self-care and impact of LE on HRQOL should be addressed [53]. Various studies were conducted to assess the safety of exercises regarding the BCRL risk reduction or the risk of developing BCRL; showing the advantages and disadvantages based on intensity and duration of the exercises [41,42,45]. Many studies demonstrated that all types of exercises are safe, effective and can improve the quality of life among BCRL survivors [33,37, 41,45,]. In addition, the recent review on the efficacy of exercises for BCRL revealed that there was not effect of exercises mode (aerobic, resistance, or mixed) and duration of intervention on BCRL status or HRQOL (MD ranging between -0.2 and 0.1 (P values.22). The authors recommended more studies to support or refute the current standard care which including wearing compression sleeves during decongestive exercises [50]. Moreover, the review assessing the efficacy of exercises mode and frequency revealed that moderate- or vigorous-intensity versus mild-intensity exercise programs should slightly improve HRQOL of patients which include physical, psychosocial and fatigue. The authors recommended a study that investigating long-term outcomes of exercises focused on mode, frequency, ISL stage and duration [49]. The quality of this review was graded low because of the heterogeneity of exercises regimens, variation of tools used to assess patient’s quality of life scores, and the included studies RCTs had high risk of biases [49,50]. Moreover, medically supervised exercises programs were recommended to be implemented for BCRL to increase adherence and potentially prolong survivorship. ACSM guideline for supervised exercises include four main types of exercises, resistance or stretching exercises, aerobic exercises, mixed exercises and decongestive exercises [38]. The exercises prescription starts with slow progressive gentle exercises; increased exercises frequency from moderate to rigorous about 3 to 5 times/week; each session comprises approximately 30- 60 minutes depending to exercises physician appreciation. In addition, 1-RM is performed first, moderate aerobic exercises include 8-15 repetitions, 65 -75% of Heart Rate Reserve (HRR) and stretching or resistance include 2 series of 5- 12 repetitions with high intensity of 75 -90% of HHR and mixed aerobic depend on 1-RM calculation [38,43]. 
Among nine studies included in the review; we accounted different interventions among which complied with ACS, ISL and ACSM guidelines for the supervised exercises prescriptions for LE. These recommendations were based on evaluation of 1-RM, mode, frequency and duration [23,30,38]. But the heterogeneity related to the variations of exercises types could not help us for quantifying the level of evidence based on ISL stages. The studies comparing exercises mode, frequency and 1-RM were published in recent reviews showing that high frequency exercises were associated with LE volume reduction and improved HRQOL [49,50]. In addition, serious side effects of exercises were not reported in many studies included in our review; this may be explained by the fact that the studies considered only those with stable ISL, and who were screened to be eligible for physical activities. Moreover, the review conducted by Romerberg, et al; with 30 studies on effects of exercises whereby exercises prescriptions were divided into high-medium and low frequency groups [76]. The authors concluded that resistance exercises combined with standard care maybe beneficial for BCRL patients in improving HRQOL and upper limbs strength [76]. Our review confirmed the same findings; however, measuring of dimensions of quality of life was limited given the variability used to quantify the HRQOL score. Further study should be conducted to correlate exercises mode, intensity and duration with ISL stages and functional, psychosocial and emotional dimensions of QOL scores for evidence-based recommendation in clinical practice. 
8.       Limitations 
ROM based physical activities outcomes, the correlation of the effects of the exercises based on ISL stages, and subgroups-based analysis focused on tools used to measure the efficacy of exercises across the intervention and control arms were not reported. The meta-analysis of the above limitations was not conducted because of significant heterogeneity within the studies and these results were reported narratively. Additionally, the results did not consider exercises in patients on pneumatic pumps and other types of unestablished conservative therapies for BCRL such as yoga, acupuncture, Chinese medicine, and African traditional medicine, chemotherapy for LE or paediatrics-based exercises. In addition, finding from these meta-analyses should be considered in light of small sample sizes and few studies evaluating supervised exercises versus no supervised in management of BCR. About half of the studies included in this review were graded low quality of evidence for primary outcomes and moderate for secondary outcome measured. The exercises mode and frequency and duration varied according to setting and author’s flexibility. Suggesting threat to internal validity. Study samples included with the females initially with a stable upper limb LE. Since many subjects were used to routine standardized exercises, the adherence should be maximized by the fact that safety and feasibility were generally compromised before participating into the trials. As such, the effectiveness, relevance, adherence, side effects, and safety of exercises among those patients with severe LE could not be assessed in this study and the work of this nature could be considered for further assessment. Other bias should be introduced by the lack blinding of patient’s outcomes assessors in many studies. While blinding is not always possible in exercises interventional studies or in using of compression sleeves. Moreover, potential bias may be likely by objectives assessment of LE for primary outcomes and publication bias was not addressed with funnel plot because of number of studies less than 10; and the review included only peer-reviewed articles. It is likely that the omission of unpublished studies and other well conducted observational studies resulted in publication bias. This because the studies with negative results are less likely to be published and the inclusion of these types of studies may reduce the threats to internal validity. The generalizability of these findings to other population with severe stage of LE should be established with enough high level of evidence. 
9.       Conclusion 
The findings from our meta-analysis revealed that supervised medically exercises combined with CDT are more effective in reducing LE volume and potentially improve HRQOL among BCRL survivors. The studies on the effect of the supervised exercises on LE survivor’s adherence and the exercises mode and frequency are recommended to extend the level of evidence. The healthcare providers should consider ISL guideline for supervised exercise prescription in clinical settings. These including screening for safety and comorbidities. The trials to strengthen uniformity of clinical guidelines and integration of supervised exercises in community based-clubs should be enforced to improve adherence. 
10.   Author’s Contributions 
·         Designing, search strategy, registering of review, protocol writing, data extraction, risk of bias assessment, critical appraisal, data analysis, interpretation of final report and writing of manuscript
·         Data collection, edition, critical appraisal, data extraction, risk of bias assessment, quality improvement.
·         Data collection, edition, critical appraisal, data extraction, risk of bias assessment, quality improvement.
·         Designing, search strategy, registering of review, protocol writing, data extraction, risk of bias assessment, critical appraisal, data analysis, interpretation of final report and writing of manuscript; 
11.    Potential Conflicts of Interest: The author indicated no potential conflicts of interest. 
12.   Acknowledgments 
The authors acknowledge Prof. Vikash Sewram of African Cancer Institute for supporting the initial phase of the project. Prof. Delva Shamly and Colleen Marco for supporting in sharing their expertise in cancer rehabilitation and management in Africa. Dr. Andre Bulabula for search strategy and methodology guidance; Dr. Landry Kabego for statistical analysis.



Figure 1: PRISMA flow chart.





Figure 2: Forest plot of comparison: NSE vs SE: NSE vs SE. Outcome: Age.





Figure 3: Forest plot of comparison: NSE vs SE. Outcome: lymphedema volume reduction.





Figure 4: Forest plot of comparison: NSE vs SE. Outcome: improved HRQOL.







Figure 5: Risk of bias assessment. Legends: NSE= No supervised exercises, SE= supervised exercises, P= p value, DASH= Disabilities of the Arm, Shoulder, and Hand; EORTC QLQ= European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; LCM= limb circumference measurement. 

Authors/years Country

Design/outcomes

Exercises program/types

Sample intervention

Sample control

Mean (SD) Age,

Mean reduction intervention

 Mean (SD) Control

P value

Conclusion

Hayes, et al. 2009, Australia

RCT/LCM, QOL, BIS, perometry

Supervised versus no, resistance, mixed, aero, 30-5/3 times daily. 12 weeks

16 F

16 F

I: 59(7) C:60(11)

 0.2(0.7)

0.01(0.09)

0.75 0.88

Exercise is beneficial for physical and psychosocial/no difference

McClure, et al. 2010

QOL, AROM, SF36

Supervised, biweekly, 1h, 17 weeks

16 F

16 F

I:57.7(2.9) C:59(2.1)

22.86(7.51)

12.57(7.30)

0.19

Adherence was in TG, improved physical and emotional of TG.

Bushan, et al. 2016, Australia

RCT, aero and resistance on AROM, QOL, BIS, self-report

Supervised versus no; Resistance and aero, 150 weekly, 3-5times,12 weeks,

20 F

21 F

56

6.5(…) DASH 15.3

5.1 DASH 14.8

0.48 0.5

No difference between 2 groups

Kim, et al. 2010, Korea

RCT, supervised exercise +CDT versus No supervised. LCM tool. SF-36, LVR.

Resistance, 15min/d, 5 days, 8 weeks.

20 F

20 F

I: 50.5(10.58) C: 50.9(9.15)

16.74(1.01) SF-36: 66.75(13.40)

12.76(-1.4) SF-36: 60.24(12.73).

0.5

Supervised exercises reduce LE and improve QOL.

Irdelsel, et al. 2007

RCT, supervised s no; CG. VAS, LVR/AROM

3 to 6 months, 3 times daily, resistance and aerobic,

10 F

9 F

51.6(8.8)

3(1.3)

2.7(2.0)

-

Supervised exercises plus compression is effective than CDT and non-Supervised exercises.

Buragadda, et al. India. 2015

RCT/ LVR, QOL. LCM. DASH.

Remedial, glenohumeral, deep breathing, 5 times weekly, 6 weeks. Versus standard of care without supervision

30 F

30 F

I: 56.3(3.3) C: 56(3.5)

24.6(1.9) DASH 5(1.1)

23(2.6) DASH 2(0.5).

 

CDT and home supervised program reduce LV and improve QOL.

Melan, 2016, India

RCT/HRQOL EORTC QLQ C 30 function VAS

IDEM /VAS

30

30

I: 56.3(3.3). C: 56(3.5)

81.83(1.42) VAS: 2.93(0.87)

85.27(1.98) VAS: 1.40(0.50)

 

Supervised remedial exercises program adjunct to CDT improve HRQOL.

Schmitz et al. 2009, SA

RCT/ LVR, water displacing

Supervised weight lifting exercises, 90 mints twice weekly, 12 weeks.

70

69

I:56(9) C: 58(10)

-0.51(0.80)

-0.22(0.71)

0.03

Progressing weight lifting moderate to rigorous reduce LV.

Sener et al. 2017, Turkey

RCT/LVR, LCM. DASH-30

Supervised pilates exercises versus No, 5-8 persons 3 times a week/8 weeks.

30

30

I: 53.2(7.7) C: 54.03(12.57)

1.24(0.43). DASH 37.99(15.02

0.12(-0.2) DASH 32.15(12.11)

0,01

Supervised clinical pilate exercises are safe and could be considered for the programs.

Table 1: List of Included Studies.

Patient or population: patients with

Settings: Australia, USA, Turkey, South Africa

Intervention: Lymphoma volume reduction

Outcomes

Illustrative (95% CI)

 Comparative risks*

Relative effect (95% CI)

No of Participants (studies)

Quality of the evidence (GRADE)

Comments

 

Assumed risk

Corresponding risk

 

 

 

 

 

Control Lymphoma reduction volume

Lymphedema volume reduction

 

The mean lymphedema volume reduction in the intervention groups was 1.35 higher (0.63 to 2.07 higher)

 

371 (6 studies)

⊕⊕⊝⊝ low1,2

 

Improved HRQOL

 

The mean improved hrqol in the intervention groups was 3.02 higher (2.59 to 3.45 higher)

 

201 (4 studies)

⊕⊕⊕⊝ moderate3

 

Mean age of developing Lymphedema

 

The mean age of developing lymphedema in the intervention groups was 0.34 lower (1.23 lower to 0.56 higher)

 

483 (9 studies)

⊕⊕⊕⊝ moderate3

 

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval;

GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

1Other bias were more than 75% 2Heterogeneity was more than 75%

             


Table 2: Risk of Bias Assessment.

  1. Greene AK, (2015) Epidemiology and Morbidity of Lymphedema. Springer International Publishing pp 33-44.
  2. Földi E (2006) Földi. Földi's textbook of lymphology for physicians and lymphedema therapists. (2nd ed.) Elsevier, Munich; 2006.
  3. Norton School of Lymphatic Therapy. Course manual: Manual lymph drainage/complete decongestive therapy certification training. Norton School of Lymphatic Therapy, New Jersey (2008).
  4. Krok-Schoen JL, Oliveri JM, Kurta ML, Paskett ED (2015) Breast cancer-related lymphedema: risk factors, prevention, diagnosis and treatment. Breast Cancer Management 4: 41-51.
  5. Oren Cheifetz, Louise Haley (2010) Management of secondary lymphedema related to breast cancer. Can Fam Physician 56: 1277-1284.
  6. Fu MR, Ridner SH, Hu SH, Stewart BR, Cormier JN, et al. (2013) Psychosocial impact of lymphedema: a systematic review of literature from 2004 to 2011. PsychoOncology 22: 1466-1484.
  7. Pusic AL, Cemal Y, Albornoz C, Klassen A, Cano S, et al. (2013) Quality of life among breast cancer patients with lymphedema: a systematic review of patient-reported outcome instruments and outcomes. Journal of Cancer Survivorship 7: 83-92.
  8. Stout NL, Pfalzer LA, Springer B, Levy E, McGarvey CL, et al. (2012) Breast cancer-related lymphedema: comparing direct costs of a prospective surveillance model and a traditional model of care. Phys Ther 92 : 152-163.
  9. Fu MR, Deng J, Armer JM (2014) Putting evidence into practice: cancer-related lymphedema (Evolving Evidence for Treatment and Management From 2009-2014). Clinical Journal of Oncology Nursing 18: 68-79.
  10. Shaitelman SF, Cromwell KD, Rasmussen JC, Stout NL, Armer JM, et al. (2015) Recent progress in the treatment and prevention of cancerrelated lymphedema. CA: A Cancer Journal for Clinicians 65: 55-81.
  11. Binkley JM, Harris SR, Levangie PK, Pearl M, Guglielmino J, et al. (2012) Patient perspectives on breast cancer treatment side effects and the prospective surveillance model for physical rehabilitation for women with breast cancer. Cancer 118: 2207-2216.
  12. Beesley VL, Rowlands IJ, Hayes SC, Janda M, O'Rourke P, et al. (2015) Incidence, risk factors and estimates of a woman's risk of developing secondary lower limb lymphedema and lymphedema-specific supportive care needs in women treated for endometrial cancer. Gynecol Oncol 136: 87-93.
  13. Ribeiro Pereira ACP, Koifman RJ, Bergmann A (2017) Incidence and risk factors of lymphedema after breast cancer treatment: 10 years of follow-up. Breast 36: 67-73.
  14. Kwan ML, Lee VS, Roh JM, Ergas IJ, Zhang Y, et al. (2015) Race/ethnicity, genetic ancestry, and breast cancer-related lymphedema. Cancer Res 75: 3724-3724.
  15. LCA (2015) Lymphoedema Referral and Management Guidelines. London Cancer Alliance.
  16. Lymphoedema Framework. Best Practice for the management of lymphoedema. International consensus. London: MEP ltd, 2006.
  17. Jain MS, Danoff JV, Paul SM (2010) Correlation between bioelectrical spectroscopy and perometry in assessment of upper extremity swelling. Lymphology 43: 85-94.
  18. Taylor R, Jayasinghe UW, Koelmeyer L, Ung O, Boyages J (2006) Reliability and validity of arm volume measurements for assessment of lymphedema. Physical Therapy 86: 205-214.
  19. Shaitelman SF, Cromwell KD, Rasmussen JC, Stout NL, Armer JM, et al. (2015) Recent progress in the treatment and prevention of cancerrelated lymphedema. CA: A Cancer Journal for Clinicians 65: 55-81.
  20. Lyman GH, Temin S, Edge SB, Newman LA, Turner RR, et al. (2014) Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. J ClinOncol 32: 1365-1383.
  21. Kwan ML, Darbinian J, Schmitz KH, Citron R, Partee P, et al. (2010) Risk factors for lymphedema in a prospective breast cancer survivorship study: The Pathways Study. Archives of surgery 145: 1055-1063.
  22. Brouillard P, Boon L, Vikkula M (2014) Genetics of lymphatic anomalies. J Clin Invest 124: 898-904.
  23. International Society of Lymphology (2013) The diagnosis and treatment of peripheral lymphedema: 2013 Consensus Document of the International Society of Lymphology. Lymphology 46: 1.
  24. Dayes, Whelan TJ, Julian JA, Parpia S, Pritchard KI, et al. (2013) Randomized Trial of Decongestive Lymphatic Therapy for the Treatment of Lymphedema in Women with Breast Cancer. Journal of Clinical Oncology 31: 3758-3763.
  25. Lasinski BB (2013) Complete Decongestive Therapy for treatment of lymphedema. Semin Oncol Nurs 29: 20-27.
  26. Armer JM, Feldman JL, Ostby PL, Thrift KM, Lasinski BB, et al. (2016) Simplifying evidence-based management of breast cancer-related lymphedema. Expert Review of Quality of Life in Cancer Care 1-14.
  27. Lane KN, Dolan LB, Worsley D, McKenzie DC (2007) Upper extremity lymphatic function at rest and during exercise in breast cancer survivors with and without lymphedema compared with healthy controls. J ApplPhysiol 103: 917-925.
  28. Gautam AP, Maiya AG, Vidyasagar MS (2011) Effect of home-based exercise program on lymphedema and quality of life in female post mastectomy patients: pre-post intervention study. J Rehabil Res Dev 48: 1261-1268.
  29. Jeffs E, Wiseman T (2013) Randomised controlled trial to determine the benefit of daily home-based exercise in addition to self-care in the management of breast cancer-related lymphoedema: a feasibility study. Supportive Care in Cancer 21: 1013-1023.
  30. Doyle C, Kushi LH, Byers T, Courneya KS, Demark-Wahnefried W, et al. (2013) Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices. CA: a Cancer Journal for Clinicians 56: 323-353.
  31. Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvao DA, et al. (2010) American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc 42: 1409-1426.
  32. Dorothy W, Wendy DW (2011) Updated Evidence in Support of Diet and Exercise Interventions in Cancer Survivors. Acta Oncol 50: 167-178.
  33. Furmaniak AC, Menig M, Markes MH (2016) Exercise for women receiving adjuvant therapy for breast cancer. Cochrane Database Syst Rev CD005001.
  34. Ahmed RL, Thomas W, Yee D, Schmitz KH (2006) Randomized controlled trial of weight training and lymphedema in breast cancer survivors. J ClinOncol 24: 2765.
  35. Milne HM, Wallman KE, Gordon S, Courneya KS (2008) Effects of a combined aerobic and resistance exercise program in breast cancer survivors: a randomized controlled trial. Breast Cancer Res Treat 108: 279-288.
  36. Sagen A, Kåresen R, Risberg MA (2009) Physical activity for the affected limb and arm lymphedema after breast cancer surgery. A prospective, randomized controlled trial with two years follow-up. Acta Oncol 48: 1102.
  37. Singh B, Disipio T, Peake J, Hayes SC (2016) Systematic Review and Meta-Analysis of the Effects of Exercise for Those with Cancer-Related Lymphedema. Arch Phys Med Rehabil 97: 302.
  38. Schmitz KH, Courneya KS, Matthews C, et al. (2010) American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc 42: 1409-1426.
  39. Courneya KS, Segal RJ, Mackey JR, et al. (2007) Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J Clin Oncol 25: 4396-4404.
  40. Kwan ML, Cohn JC, Armer JM, Stewart BR, Cormier JN (2011) Exercise in patients with lymphedema: a systematic review of the contemporary literature. J Cancer Surviv 5: 320-336
  41. Keilani M, Hasenoehrl T, Neubauer M, Crevenna R (2016) Resistance exercise and secondary lymphedema in breast cancer survivors-a systematic review. Support Care Cancer 24: 1907-1916.
  42. Kilbreath SL, Refshauge KM, Beith JM (2012) Upper limb progressive resistance training and stretching exercises following surgery for early breast cancer: a randomized controlled trial. Breast Cancer Res Treat 133: 667-676.
  43. Schmitz KH (2010) Balancing lymphedema risk: exercise versus deconditioning for breast cancer survivors. Exerc Sport Sci Rev 38: 17-24.
  44. Speck RM, Courneya KS, Mâsse LC, Duval S, Schmitz KH (2010) An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. J Cancer Surviv 4: 87-100.
  45. Schmitz KH, Speck RM (2010) Risks and benefits of physical activity among breast cancer survivors who have completed treatment. Womens Health (Lond Engl) 6: 221-238.
  46. National Lymphedema Network Position statement of the National Lymphedema Network: training of lymphedema therapists.
  47. Moseley AL, Piller NB, Carati CJ (2005) The effect of gentle arm exercise and deep breathing on secondary arm lymphedema. Lymphology 38: 136-145.
  48. Kwan ML, Cohn JC, Armer JM, Stewart BR, Cormier JN (2011) Exercise in patients with lymphedema: a systematic review of the contemporary literature. J Cancer Surviv 5: 320-336.
  49. Mishra SI, Scherer RW, Snyder C, Geigle PM, Berlanstein DR, et al. (2012) Exercise interventions on health-related quality of life for people with cancer during active treatment. Cochrane Database Syst Rev 15: CD008465.
  50. Stout NL, Baima J, Swisher AK, Winters-Stone KM, Welsh J, et al. (2017) A Systematic Review of Exercise Systematic Reviews in the Cancer Literature. (2005 - 2017). PM R 9: S347-S384.
  51. Heyward VH (2006) Advanced Fitness Assessment and Exercise Prescription.
  52. Douglass J, Graves P, Gordon S (2016) Self-Care for Management of Secondary Lymphedema: A Systematic Review. PLoS Negl Trop Dis 10: e0004740.
  53. Brown JC, Cheville AL, Tchou JC, Harris SR, Schmitz KH (2014) Prescription and Adherence to Lymphedema Self-Care Modalities among Women with Breast Cancer-Related Lymphedema. Support Care Cancer 22: 135-143.
  54. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6: e1000097.
  55. Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org
  56. Buragadda S, Alhusaini AA, Melam GA, Arora N (2015) Effect of complete decongestive therapy and a home program for patients with post mastectomy lymphedema. J Phys Ther Sci 27: 2743-2748.
  57. Launois R, Megnigbeto AC, Pocquet K, Alliot F (2002) A specific quality of life scale in upper limb lymphedema: the ULL-27 questionnaire. Lymphology 35: 1-760&181-187.
  58. Melam GR, Buragadda S, Alhusaini AA, Arora N (2016) Effect of complete decongestive therapy and home program on health- related quality of life in post mastectomy lymphedema patients. BMC Womens Health 16: 23.
  59. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, et al. (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Nat Cancer Inst 85: 365-376.
  60. Hayes SC, Reul-Hirche H, Turner J (2009) Exercise and secondary lymphedema: safety, potential benefits, and research issues. Med Sci Sports Exerc 41: 483-489.
  61. McClure MK, McClure RJ, Day R, Brufsky AM (2010) Randomized controlled trial of the Breast Cancer Recovery Program for women with breast cancer-related lymphedema. Am J Occup Ther 64: 59-72.
  62. Buchan J, Janda M, Box R, Schmitz K, Hayes S (2016) A Randomized Trial on the Effect of Exercise Mode on Breast Cancer-Related Lymphedema. Med Sci Sports Exerc 48: 1866-1874.
  63. Kim DS, Sim YJ, Jeong HJ, Kim GC (2010) Effect of active resistive exercise on breast cancer-related lymphedema: a randomized controlled trial. Arch Phys Med Rehabil 91: 1844-1848.
  64. Schmitz KH, Ahmed RL, Troxel A, Cheville A, Smith R, et al. (2009) Weight lifting in women with breast-cancer-related lymphedema. N Engl J Med 13: 664-673.
  65. Irdesel J, Çeliktas SK (2007) Effectiveness of Exercise and Compression Garments in the Treatment of Breast Cancer Related Lymphedema. Turkish Journal of Physical Medicine & Rehabilitation / Turkiye 53: p16.
  66. Şener HO, Malkoç M, Ergin G, Karadibak D, Yavuzşen T (2017) Effects of Clinical Pilates Exercises on Patients Developing Lymphedema after Breast Cancer Treatment: A Randomized Clinical Trial. J Breast Health 13: 16-22.
  67. DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, et al. (2014) Cancer treatment and survivorship statistics, 2014. CA: a cancer journal for clinicians 64: 252-271.
  68. Anderson BO, Ilbawi AM, El Saghir NS (2015) Breast cancer in low and middle-income countries (LMICs): a shifting tide in global health. Breast J 21: 111-118.
  69. Curado MP (2011) Breast cancer in the world: incidence and mortality. Saludpública de México 53: 372-384.
  70. Fan L, Strasser-Weippl K, Li J, Finkelstein DM, Yu K, et al. (2014) Breast cancer in China. The lancet oncology 15: e279-e289.
  71. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, et al. (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International journal of cancer 136: E359-E386.
  72. Jemal A, Bray F, Forman D, O'Brien M, Ferlay J, et al. (2012) Cancer burden in Africa and opportunities for prevention. Cancer 118: 4372-4384.
  73. Youlden DR, Cramb SM, Dunn NA, Muller JM, Pyke CM, et al. (2012) The descriptive epidemiology of female breast cancer: an international comparison of screening, incidence, survival and mortality. Cancer epidemiology 36: 237-248.
  74. Imran OM, Folakemi O, Timothy RR, Joe H, Jean-Marie D (2013) Challenges and opportunities in cancer control in Africa: a perspective from the African Organisation for Research and Training in Cancer. Lancet Oncol 14: e142-e151.
  75. Krok-Schoen JL, Oliveri JM, Kurta ML, Paskett ED (2015) Breast cancer-related lymphedema: risk factors, prevention, diagnosis and treatment. Breast Cancer Management 4: 41-51.
  76. Romesberg M, Tucker A, Kuzminski K, Tremback-Ball A (2017) The Effects of Resistance Exercises on Secondary Lymphedema Due to Treatment of Breast Cancer: A Review of Current Literature. Journal of Womenʼs Health Physical Therapy 41: 91-99.

Citation: Milambo JPM, Ndayisaba L, Kabego L, Tshilombo KV, Tamuzi JL (2018) The Effects of Supervised Exercises Program on upper limb dysfunction and Quality of Life in breast cancer survivors following different treatment strategies: Meta-Analysis. J Oncol Res Ther: JONT-146. DOI: 10.29011/2574-710X. 000046

free instagram followers instagram takipçi hilesi