• clinical practice guidelines;
  • breast cancer;
  • rehabilitation;
  • qualitative appraisal


  1. Top of page
  2. Abstract
  6. Acknowledgements
  7. Note Added in Proof


Despite strides in early detection and management of breast cancer, the primary treatments for this disease continue to result in physical impairments for some of the nearly 3 million people diagnosed annually. Over the past decade, evidence-based clinical practice guidelines (CPGs) have been developed with goals of preventing and ameliorating these impairments. However, translation of these guidelines into clinical practice needs to be accelerated.


Relevant health science databases (2001-2011) were searched to identify CPGs on breast cancer rehabilitation for the following impairments: upper extremity restrictions, lymphedema, pain, fatigue, chemotherapy-induced peripheral neuropathy, treatment-related cardiotoxicity, bone health, and weight management.


Recommendations from 19 relevant CPGs were first summarized by impairment within tables; commonalities across guidelines, within each impairment, were then synthesized within the article. The CPGs were rated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II); wide variability was noted in rigor of development, clarity of presentation, and stakeholder involvement. The most rigorous and comprehensive of those rated was the adult cancer pain guideline from the Scottish Intercollegiate Guidelines Network.


Based on a large body of evidence published in recent years, including randomized trials and systematic reviews, there is an urgent need for updating the guidelines on upper extremity musculoskeletal impairments and lymphedema. Furthermore, additional research is needed to provide an evidence base for developing rehabilitation guidelines on management of other impairments identified in the prospective surveillance model, eg, arthralgia. Cancer 2012;118(8 suppl):. © 2012 American Cancer Society.

Despite important strides in recent years in early detection1, 2 and management of breast cancer,3-5 the primary treatments for this disease (surgery, radiation, and chemotherapy) continue to lead to significant morbidity for some of the nearly 3 million women (and men) around the world who are diagnosed annually.6 In addition to the profound psychosocial impact of receiving a breast cancer diagnosis, a number of physical impairments commonly result from the treatments designed to save or prolong the lives of those affected. These include impairments of upper extremity range of motion and strength, upper extremity and/or breast lymphedema, pain, fatigue, loss of sensation, and reduction in levels of physical activity and health-related quality of life.7-10

Despite the wide array of physical impairments that can occur after breast cancer treatments, there is little information in the peer-reviewed literature about how best to manage these impairments. Particularly lacking in the literature are recent, evidence-based, clinical practice guidelines (CPGs) on upper extremity impairments and arthralgia. CPGs are defined as “statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options.”11(p29) Critical reviews of practice guidelines have shown them to vary considerably in the strength of evidence used in their development, the search methods employed to gather the evidence, and the demonstration of links between the evidence gleaned and the resulting practice recommendations.12-14

With publication of the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument in 200315 and recent expansion and improvement of the tool as the AGREE II,16, 17 it is now possible to address this variability in guideline quality by systematically evaluating key factors in guideline development. The AGREE II comprises 23 items within 6 domains: 1) scope and purpose; 2) stakeholder involvement; 3) rigor of development; 4) clarity of presentation; 5) applicability; and 6) editorial independence.18 Each item is rated on a 7-point scale from strongly disagree to strongly agree; 2 overall appraisal items assess the overall quality of the guideline and whether it should be recommended for practice.

Each guideline is rated by at least 2 appraisers, with other raters added if there is major discordance in 1 domain or medium-level discordance in more than 2 domains.18 Aggregate scoring across domains is not recommended; instead, the 2 global appraisal items are used to rate overall quality. Table 1 provides an example of how to calculate the score for Domain 1: Scope and Purpose.

Table 1. Scoring the AGREE II: Calculating Domain Scores18a
 Item 1Item 2Item 3Total
  • a

    AGREE II indicates Appraisal of Guidelines for Research and Evaluation II.

  • Domain scores are calculated by summing up all the scores of the individual items in a domain and by scaling the total as a percentage of the maximum possible score for that domain. Example: If 4 appraisers give the above scores for Domain 1 (scope and purpose)

  • Maximum possible score = 7 (strongly agree) × 3 items × 4 appraisers = 84

  • Minimum possible score = 1 (strongly disagree) × 3 (items) × 4 (appraisers) = 12

  • The scaled domain score will be:

Appraiser 156617
Appraiser 266719
Appraiser 32429
Appraiser 43328

Cited in more than 200 publications, the AGREE has been used by the National Institute for Health and Clinical Excellence19, 20 and other policy organizations in reviewing CPGs.21 According to a recent Lancet commentary, updating of the AGREE to the AGREE II “will continue to make an important contribution to improving the quality of clinical care.”22

The overall goal of this article was to identify and review CPGs related to the assessment and management of physical impairment outcomes of having had breast cancer and/or from the interventions used to treat the disease. Specific objectives were 1) to summarize and synthesize recommendations from recent practice guidelines (2001-2011) in order to provide guidance to consumers, rehabilitation clinicians, and health care funding agencies on evidence-based rehabilitation for persons living with breast cancer; 2) to rate the methodological quality of current practice guidelines using the AGREE II; and 3) to provide recommendations for updating current guidelines and for developing additional, evidence-based practice guidelines related to breast cancer rehabilitation.

We focused on impairments included in the Prospective Surveillance Model for Physical Rehabilitation for Women with Breast Cancer23: upper extremity restrictions, lymphedema, pain, fatigue, chemotherapy-induced peripheral neuropathy (CIPN), treatment-related cardiotoxicity, and bone health. Although there were no CPGs on weight management, per se, we located some evidence-based recommendations on weight control that appeared in other guidelines or published reports.


  1. Top of page
  2. Abstract
  6. Acknowledgements
  7. Note Added in Proof

Search Strategies

We performed an initial search of MEDLINE, Google, Google Scholar, and the Physiotherapy Evidence Database (PEDro) from 2001 through April 2, 2011. This was followed by a more extensive search by a University of British Columbia health sciences reference librarian for gray literature, using Grey Matters and Intuit, and of Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Embase (OvidSP) from 2001 to May 5, 2011. Search terms were used for the concepts of breast cancer, rehabilitation, and guidelines. Based on both sets of searches, 17 organizations that publish breast cancer guidelines were identified and are listed in Table 2.19, 20, 24-39

Table 2. Organizations Searched for Relevant Guidelines, Country of Origin, and Year of Most Recent Update for any Breast Cancer Guideline
Guideline Publisher (Reference Number)Country of OriginAdditional Information or Referral to Another CPG DatabaseLast Update
  1. CPG indicates clinical practice guideline.

Agency for Healthcare Research and Quality (AHRQ)24United States of AmericaRefers readers to National Guideline Clearing House291994
American Society of Clinical Oncology (ASCO)25United States of AmericaIncludes 9 breast cancer CPGs (2001-2011) but none related to rehabilitation2011
British Columbia Cancer Agency (BCCA)26CanadaRefers readers to CMAJ breast cancer CPGs262011
Canadian Breast Cancer Network (CBCN)27CanadaIncludes only the Breast Cancer, Pregnancy, and Breastfeeding CPG from Society of Obstetricians and Gynecologists of Canada2002
Cancer Care Nova Scotia28CanadaRefers readers to CMAJ breast cancer guidelines26 and Cancer Care Ontario guidelines242005
Cancer Care Ontario29CanadaPDF for The Treatment of Lymphedema related to Breast Cancer2003
Canadian Medical Association (CMA) Infobase30CanadaIncludes 22 breast cancer CPGs (but none related to rehabilitation)2008
Canadian Medical Association Journal (CMAJ) Breast Cancer Practice Guidelines31CanadaSixteen breast cancer CPGs, including no. 11: Lymphedema2005
European Society for Medical Oncology (ESMO)32EuropeIncludes 3 breast cancer CPGs, 1 with reference to lymphedema2010
National Comprehensive Cancer Network (NCCN)33United States of AmericaEight breast cancer CPGs, but nothing related to rehabilitation. CPGs on cancer-related fatigue and adult cancer pain will be reviewed.2011
National Guideline Clearing House34United States of America  
  Includes 215 breast cancer CPGs; all rehabilitation-related CPGs captured via other Web sites2011
National Health and Medical Research Council (NHMRC)35AustraliaRehabilitation-related information included in the CPGs on management of early and advanced breast cancer2001
National Health Service (NHS) Evidence–National Library of Guidelines36United KingdomIncludes breast cancer CPGs from NICE32, 33 and SIGN352011
National Institute for Health and Clinical Excellence (NICE)19, 20United KingdomRehabilitation-relevant information in 2 CPGs: breast cancer (early and locally advanced) and breast cancer (advanced)2009
New Zealand Guidelines Group37New ZealandCPG on management of early breast cancer2009
Public Health Agency of Canada38CanadaRefers to CMA,25 CMAJ,26 and BCCA20 breast cancer CPGs2011
Scottish Intercollegiate Guidelines Network39United KingdomRelevant information in CPG 106: Control of pain in adults with cancer2007

Practice guidelines were included if they focused on breast cancer–related upper extremity physical impairments, upper extremity and/or breast lymphedema, pain, fatigue, CIPN, cardiotoxicity, or bone health. Because of the limited number of guidelines related solely to breast cancer in the latter categories, CPGs related to generic cancer pain, fatigue, CIPN, cardiotoxicity, or bone health were included also. In addition, we retrieved several, evidence-based recommendations related to weight management in breast cancer. Other inclusion criteria for guidelines were publication between 2001 and 2011, either in a peer-reviewed journal and/or endorsed by a national/multinational government agency or health professional provider group, and available in English. We did not include guidelines pertaining specifically to metastatic breast cancer.

Titles were screened by the first author (S.R. Harris) and, if there was uncertainty based on the title, abstracts or quick reference guides were then screened. For the more generic cancer guidelines, tables of contents were searched for relevant headings or subheadings, eg, upper extremity impairment, lymphedema, pain, fatigue, and rehabilitation.

Summaries and Syntheses of Guideline Recommendations

To summarize guideline recommendations across the various CPGs included in this review (Objective 1), the recommendations as written in the original guidelines were grouped for each of the major categories of interest and presented in tables: upper extremity impairments, lymphedema, pain, and fatigue. An additional table summarizes recommendations for CIPN, cardiotoxicity, bone health, and weight management; the weight management recommendations were based on 2 breast cancer follow-up CPGs and an evidence-based guide on nutrition and physical activity during and after cancer treatment.

Evaluation of Published Guidelines

To address the second objective of this article, each CPG included for review in the major impairment areas was evaluated using the AGREE II.18 Ten of the cancer-related practice guidelines had been reviewed previously with the AGREE II by the Cancer Guidelines Resource Centre, an initiative of the Cancer Guidelines Advisory Group of the Canadian Partnership Against Cancer,40 and are available on their Web site; those scores were used for this article. For the 9 guidelines not previously reviewed by the guidelines resource center, the recommendations from the AGREE II manual were followed with at least 2 authors independently rating each. The AGREE II concordance calculator was used to examine rater concordance.

Prior to using the AGREE II to appraise the guidelines included in this article, its reliability was assessed. All 4 author-appraisers first undertook the online AGREE II training. To establish inter-rater agreement, 2 breast cancer guidelines unrelated to physical impairments41, 42 were then independently rated by each of the 4 reviewers. According to the decision rules accompanying the concordance calculator, no further action is required if overall scores (across raters) are <1.5 standard deviation (SD) in all domains. However, if there is discordance of ≥2 SD in 1 domain (major discordance) or ≥1.5 SD in 3 domains (medium discordance), further action is needed. For the first guideline evaluated to test inter-rater agreement,41 only 1 domain was found to be discordant among the 4 with ≥2 SD from the mean; discrepancies within that domain were resolved through consensus. For the second article,42 only 1 domain was found to differ by 1.58 SD, thus requiring no action.

To calibrate that agreement against a gold standard comparator, we compared our own domain appraisals for the 2 guidelines to those on the Cancer Guidelines Resource Centre Web site40 ( Our goal was to obtain ≥70% agreement. The AGREE II concordance calculator was used to derive domain scores across the 4 raters' scores. For the 12 domains rated across the 2 articles (6 domains for each article), we agreed with the published appraisals (within ±10%) on 9 of 12, for an overall percent agreement of 75%. Consequently, we determined that we had sufficient agreement to justify pooling our ratings for the 9 guidelines with the already-established ratings from the Cancer Guidelines Resource Centre Web site for the other 10 guidelines.

Recommendations for Updating Current Guidelines and for Future Guidelines

The third objective of this article, to provide recommendations for updating current guidelines and developing future practice guidelines in breast cancer rehabilitation, was based on the results stemming from the first 2 objectives: the syntheses of recommendations from current CPGs and the quality appraisal of those guidelines. Recommendations based on this third objective appear in the Discussion section.


  1. Top of page
  2. Abstract
  6. Acknowledgements
  7. Note Added in Proof

Summary of Guideline Recommendations

To address the first objective of this article, to summarize and synthesize recommendations from guidelines published between 2001 and 2011, Tables 3 through 7 provide recommendations from the CPGs reviewed. Recommendations are categorized by impairment, with corresponding guideline documents referenced. We maintained the original text from the published guidelines rather than inserting changes based on more recent evidence.

Table 3. Upper Extremity Rehabilitation Guideline Recommendations43, 44
Upper Extremity Rehabilitation
 Preoperative, bilateral upper extremity function should be assessed to provide a baseline before treatments.
 Postoperative physical therapy should begin the first day following surgery. Gentle range of motion exercises should be encouraged the first week after surgery.
 Active stretching exercises can begin week 1 after surgery, or when the drain is removed, and should be continued for 6 to 8 weeks or until full range of motion is achieved in the affected upper extremity. Women should be instructed also in scar tissue massage.
 Postoperative assessments should occur regularly up to 1 year after surgery.
 Progressive resistive exercises, that is strengthening, can begin with light weights (1-2 pounds) within 4 to 6 weeks after surgery.
Hand and Arm Care
 Careful hand and arm care—for example, proper hygiene and avoiding trauma to the arm—is important to minimize risks of infection and lymphedema.
 Specific treatment-related and host-related factors contribute to the increased risks of complications. Minimizing the extent of axillary dissection, preventing infection, and avoiding obesity, for example, may help prevent the development of lymphedema.
 Generally, injections, vaccinations, venipuncture, and intravenous access in the axillary-dissected upper extremity have been contraindicated. There is some evidence (Level V) that these restrictions can be relaxed.
 Many suggestions regarding proper hygiene and trauma avoidance for the axillary-dissected upper extremity are sensible, but there is little scientific literature to support these restrictions.
Electrotherapy Modalities
 Laser treatment, electrical stimulation, microwave, and thermal therapy are not recommended at this time due to insufficient evidence to support their use, and there are published precautions and contraindications for their use in persons with neoplasms.
 Therapeutic ultrasound is contraindicated over sites of possible metastasis in women with histories of breast cancer.
Table 4. Lymphedema Guideline Recommendations,45, 46 Evidence Report Key Opinions,29, 47 and Putting Evidence into Practice (PEP) Recommendations48
Assessment and Diagnosis of Lymphedema
 Evidence supports early lymphedema diagnosis and referral for therapies to reduce patient burden.46, 48
 Pre- and postoperative measurements of both arms are useful in the assessment and diagnosis of lymphedema. Circumferential measurements should be taken at 4 points: the metacarpal-phalangeal joints, the wrists, 10 cm distal to the lateral epicondyles, and 12 cm proximal to the lateral epicondyles.45
 Clinicians should elicit symptoms of heaviness, tightness, or swelling in the affected arm. A difference of more than 2.0 cm at any of the 4 measurement points may warrant treatment of the lymphedema, provided that tumor involvement of the axilla or brachial plexus, infection, and axillary vein thrombosis have been ruled out.45
 Additional efforts to define relevant clinical outcomes for the assessment or patients with lymphedema would be valuable.29, 47
Interventions for Lymphedema
 Practitioners may want to encourage long-term and consistent use of compression garments by women with lymphedema.45
 Compression garments should be worn from morning to night and be removed at bedtime. Patients should be informed that lymphedema is a lifelong condition and that compression garments must be worn on a daily basis. Patients can expect stabilization and/or modest improvement of lymphedema with the use of the garment in the prescribed fashion.29, 47
 The Supportive Care Guidelines Group endorses the recommendations from the Steering Committee for Clinical Practice Guidelines for the care and treatment of breast cancer. The use of compression garments is consistent with what is commonly practiced clinically.29, 47
 Compression bandaging, a systematic application of short-stretch bandages with various types of padding, is recommended for practice.48
 Complex physical therapy, manual lymph drainage, compression and massage therapy are associated with volume reductions.46
 One randomized trial has demonstrated a trend in favor of pneumatic compression pumps compared with no treatment. Further randomized trials are required to determine whether pneumatic compression provides additional benefits over compression garments alone.45
 Complete decongestive therapy, also known as complex decongestive physiotherapy and complex physical therapy, is the recommended treatment for lymphedema.48
 There is some evidence that compression therapy and manual lymph drainage may improve established lymphedema, but further studies are needed.29, 47
 There is no current evidence to support the use of medical therapies, including diuretics,29, 47, 48 benzopyrones, and selenium compounds.48
Other Considerations for Lymphedema Management
 Clinical experience supports encouraging patients to consider some practical advice regarding skin care, exercise, and body weight.45, 48
 Evidence exists that a body mass index >30 is a risk factor for lymphedema.48
 Although there is no clear relationship between high body mass index and development of secondary lymphedema following treatment for cancer, maintenance of a healthy body weight in cancer survivors should be encouraged because of the other associated health benefits.48
 The opinions are appropriate for patients with more than mild lymphedema, where the signs and symptoms are considered important from the patients' perspective.29, 47
 Immediate attention to signs of infection and prompt initiation of antibiotic therapy are critical to preventing sepsis.48
 Infection risk is essential to reduce the risk of developing or exacerbating lymphedema.46
 Conservative surgical and radiation treatment for cancer should be used to reduce the risk of secondary lymphedema.46
 Surgical techniques may be useful for a small subset of secondary lymphedema sufferers who have failed to obtain relief from less invasive measures.46
Table 5. Relevant Guideline Recommendations for Cancer-Related Pain49-55
  1. PT indicates physical therapist/physical therapy; TENS, transcutaneous electrical nerve stimulation.

Evaluation of Pain
 There are many reasons why a patient with breast cancer may experience pain. Identifying the cause and understanding the pathophysiology can lead to more effective management.49-51
 The nature and severity of pain should be carefully evaluated using the history and physical, psychosocial, and emotional assessments. Adequacy of pain relief should be evaluated regularly.49, 50-52
 The patient's self-report of pain intensity is the primary source of assessment data in all initial and subsequent evaluations.49, 50-54
 Patients with cancer pain should have treatment outcomes monitored regularly49-54 using visual analogue scales, numerical rating scales, or verbal rating scales.52-54
 Physicians, and other health care professionals, should frequently reassess pain relief, side effects, and adverse events, as well as the impact of pain and treatment on patient function and quality of life.52, 55
Management of Pain
 General Principles of Pain Management
 The first objective in the management of pain is to identify the cause and treat it whenever feasible.49, 50
 The first priority of treatment is to control pain rapidly and completely, as judged by the patient; the second priority is to prevent recurrence of pain.49-50
 Patients should be given information and instruction about pain and pain management and be encouraged to take an active role in their pain management.52, 55
 Pain treatment and goals should be tailored to the needs, desires, and circumstances of individual patients.55
 Patient and Family Education
 Development of a comprehensive, effective pain management plan includes the education and involvement of the patient and family, together with an interdisciplinary team approach.49-51, 54
 Patients and families should receive written information regarding pain management options51 and education about the range of pain control interventions available to them.52
 Brief educational interventions and pain management diaries are useful strategies that improve adherence and reduce pain intensity.55
Nonpharmacologic Interventions for Pain
 Consider nonpharmacologic interventions in conjunction with pharmacologic interventions as needed. Pain is likely to be relieved or function improved with physical modalities such as: bed, bath, and walking supports; positioning instruction; PT; energy conservation; pacing of activities; TENS, acupuncture or acupressure.49-52, 54
 Specialty consultations for improved pain management include physical/occupational therapy, rehabilitation/mobility specialty consultation.51
Table 6. Relevant Guideline Recommendations for Cancer-Related Fatigue56, 57
Screening and Evaluation for Fatigue
 Screen every patient for fatigue as vital sign at regular intervals (using a 10-point scale in which a score ≥4 = moderate fatigue). Patients with moderate to severe fatigue should be queried about their activity level, including changes in exercise or activity patterns and the influence of deconditioning.56
 There is expert consensus that patients with fatigue be screened for potentially detectable factors contributing to fatigue.57
 Before recommending an exercise program, health care providers or exercise experts (eg, physiatrist, physical therapist) should assess the conditioning level of patients.56
Interventions for Patients on Active Treatment
 Education and Counseling of Patient
 Education about fatigue and its natural history should be offered to all cancer patients but is particularly essential for patients beginning potentially fatigue-inducing treatments (eg, radiation, chemotherapy, or biotherapy).56
 In addition to education, the National Comprehensive Cancer Network panel recommends counseling for patients about general strategies (energy concentration and distraction) useful in coping with fatigue.56
 Educational interventions (including teaching, counseling, support, anticipatory guidance about fatigue patterns, coping skills training, and coaching) are “likely to be effective” in supporting positive coping in patients with fatigue and in reducing fatigue levels.57
 Physical Activity/Exercise
 It is reasonable to encourage all patients to engage in a moderate level of physical activity during and after cancer treatment, eg, 30 minutes of moderate activity most days of the week.56
 Exercising several times per week (including walking, cycling, resistance exercise, or a combination of aerobic and resistance exercise) can be effective in reducing fatigue during and following cancer treatment.57
 Some patients may require referrals to exercise specialists in fields such as physical therapy, physical medicine, or rehabilitation for assessment and an exercise prescription.56
Interventions for Patients After Treatment
 Maintain optimal level of activity.56
 Consider initiation of exercise program of both endurance and resistance exercise. It is reasonable to encourage all patients to engage in a moderate level of physical activity during and after cancer treatment,56 eg, 30 minutes of moderate activity most days of the week.
 Consider referral to rehabilitation: physical therapy, occupational therapy, physical medicine.56
 The exercise program should be individualized based on the patient's age, sex, type of cancer, and physical fitness level.56 The program should begin at a low level of intensity and duration, progress slowly, and be modified as the patient's condition changes.56
Other Considerations for Cancer-Related Fatigue
 The guidelines for fatigue are best implemented by an interdisciplinary institutional committee, including representatives from the fields of medicine, nursing, social work, physical therapy, and nutrition.56
Table 7. Nonpharmacologic Guideline Recommendations for Chemotherapy-Induced Peripheral Neuropathy, Treatment-Related Cardiotoxicity, Bone Health, and Weight Management
  1. CIPN indicates chemotherapy-induced peripheral neuropathy.

Chemotherapy-Induced Peripheral Neuropathy
 National Comprehensive Cancer Network panelists generally agreed that transcutaneous electrical nerve stimulation can be a helpful adjuvant therapy for CIPN in those with contraindications to or for whom pain medication is ineffective.59
 Acupuncture is noninvasive and relatively inexpensive and may be considered as an adjunct option in treating patients with medication-resistant CIPN.58, 59
 Panelists strongly recommended referring patients with CIPN that interferes with functioning to a physical or occupational therapist. Therapeutic intervention, education, and practical advice provided by these rehabilitation specialists can prove invaluable in helping patients to both correct CIPN-induced functional deficits and to cope with the difficulties and challenges these deficits cause in their everyday life.59
Treatment-Related Cardiotoxicity
 Patients should be encouraged to adopt a healthy lifestyle in order to protect the myocardium, including a balanced diet, moderate exercise, and smoking cessation.60
Bone Health
 Weight-bearing exercise has been associated with a decreased risk of hip fractures, probably due to a reduction in fall risk and also through modest effects on preservation of bone density.62
 Tai chi, physical therapy, and dancing are considered good options to improve balance and prevent falls.62
 Adults should aim for at least 30 minutes of moderate physical activity daily (either in 1 continuous session or in a number of shorter bursts). This activity can include a mix of weight-bearing, strength training, and balance training exercises.62
 Wearing hip protectors may prevent hip fracture in the event of a fall and can be considered for patients with a high risk for falling.62
Weight Management
 Weight management should be discussed with all breast cancer survivors.64
 Weight gain affects prognosis adversely and should be discouraged; if necessary, nutritional counseling is recommended. Regular long-term moderate to strenuous physical activity is associated with a favorable prognosis; aerobic training and weight lifting does not negatively affect the development of lymphedema.65
 Maintain a healthy body weight throughout life.66
  • Balance caloric intake with physical activity
  • Avoid excessive weight gain throughout the life cycle
  • Achieve and maintain a healthy weight if currently overweight or obese

Recommendations from the sole CPG43 (with update)44 on upper extremity impairment appear in Table 3. For lymphedema, we located 2 CPGs,45, 46 1 evidence summary,29, 47 and 1 Putting Evidence into Practice (PEP) resource (Table 4).48 According to the authors of the evidence summary, such summaries are developed when high-quality evidence is insufficient to make clinical recommendations in the form of guidelines.29, 47 Because the PEP resource on lymphedema47 did not include specific, highlighted, guideline-type recommendations (or key opinions), we extracted several statements from the section labeled “Recommended for Practice,” a weight-of evidence category described by the authors as “effectiveness is demonstrated by strong evidence from rigorously designed studies, meta-analyses, or systematic reviews.”48(p953)

In the area of cancer-related pain, only 1 CPG specifically related to breast cancer pain49 (and a published summary of it50) were located, unfortunately the oldest (2001) of the pain CPGs. An additional 5 pain CPGs that related to cancer pain in general were also appraised.51-55 Guideline recommendations relating to nonpharmacologic management of pain are included in Table 5. For cancer-related fatigue, 2 recent CPGs were included56, 57; only nonpharmacologic recommendations from these guidelines were listed (Table 6).

Of the 2 CIPN guidelines,58, 59 the more recent (2009) included more specific rehabilitation recommendations.59 For the 2 CPGs on treatment-related cardiotoxicity,60, 61 only 1 included an exercise recommendation60 (Table 7). Of the 2 guidelines on bone health,62, 63 only the more recent one (National Comprehensive Cancer Network [NCCN]) included rehabilitation-related suggestions.62 Recommendations on weight management from 2 breast cancer follow-up CPGs64, 65 and an evidence-based guide66 are also included in Table 7.

Methodological Quality of Guidelines

Tables 8 through 13 summarize the methodological quality ratings of the CPGs reviewed across the 6 AGREE II domains. For the 9 guidelines rated by the authors,29, 43-47, 49, 50, 52, 57, 59, 62 there were 22 items (of a total of 207) in which 1 appraiser's rating was an important outlier, ie, 1 rater gave the item a score of 1, and the other appraiser rated it significantly higher. The appraiser who had initially given a score of 1 was asked to re-review the guideline and change her score, if she deemed it necessary. Eleven initial scores (50% of the 22 discrepant ratings or 5.3% of the total ratings) were changed as a result of these second reviews. For those ratings that remained unchanged, the original scores were entered into the AGREE II concordance calculator to determine the overall domain ratings across appraisers.

Table 8. AGREE II Quality Assessment for Upper Extremity Rehabilitation Guidelines
AGREE II DomainUpper Extremity Rehabilitation (BCCA)43, 44a
  • AGREE II indicates Appraisal of Guidelines for Research and Evaluation II; BCCA, British Columbia Cancer Agency.

  • a

    Guideline rated by K.L. Campbell and M.L. McNeely.

Scope and purpose88.9%
Stakeholder involvement80.6%
Rigor of development75.0%
Clarity of presentation91.7%
Editorial independence12.5%
Table 9. AGREE II Quality Assessment for Lymphedema Guidelines
AGREE II DomainLymphedema (CMA)45bLymphedema (CCO)29, 47cLymphedema (ONS)48aLymphedema (NBOCC)46c
  • AGREE II indicates Appraisal of Guidelines for Research and Evaluation II; CMA, Canadian Medical Association; CCO, Cancer Care Ontario (Canada); NBOCC, National Breast and Ovarian Cancer Centre (Australia); ONS, Oncology Nursing Society.

  • a

    Guideline rated by Cancer Guidelines Resource Centre.40

  • b

    Guidelines rated by K.H. Schmitz and M.L. McNeely.

  • c

    Guidelines rated by M.L. McNeely and S.R. Harris.

Scope and purpose75.0%83.3%55.6%83.3%
Stakeholder involvement83.3%47.2%55.6%50.0%
Rigor of development66.7%58.0%42.7%59.4%
Clarity of presentation94.4%80.6%63.9%75.5%
Editorial independence75.0%16.7%16.7%20.8%
Table 10. AGREE II Quality Assessment for Cancer-Related Pain Guidelines49-55
AGREE II DomainCMA49, 50b (Canada)NCCN51a (USA)SIGN52b (Scotland)ESMO53a (Europe)CCO54a (Canada)APS55a (USA)
  • APS indicates American Pain Society; CCO, Cancer Care Ontario; CMA, Canadian Medical Association; ESMO, European Society of Medical Oncology; NCCN, National Comprehensive Cancer Network; SIGN, Scottish Intercollegiate Guidelines Network.

  • a

    Guidelines rated by Cancer Guidelines Resource Centre.40

  • b

    Guidelines rated by M.L. McNeely and S.R. Harris.

Scope and purpose72.2%41.7%88.9%22.2%86.1%80.6%
Stakeholder involvement50.0%38.9%100.0%11.1%55.6%58.3%
Rigor of development45.8%38.5%89.6%16.7%75.0%67.7%
Clarity of presentation88.9%91.7%100.0%52.8%88.9%77.8%
Editorial independence41.7%45.8%83.3%16.7%91.7%45.8%
Table 11. AGREE II Quality Assessment for Cancer-Related Fatigue Guidelines
AGREE II DomainNational Comprehensive Cancer Network (USA)56aOncology Nursing Society (USA)57b
  • AGREE II indicates Appraisal of Guidelines for Research and Evaluation II.

  • a

    Guidelines rated by Cancer Guidelines Resource Centre.40

  • b

    Guideline rated by S.R. Harris and K.H. Schmitz.

Scope and purpose66.7%77.8%
Stakeholder involvement53.7%47.2%
Rigor of development28.5%58.3%
Clarity of presentation87.0%77.8%
Editorial independence61.1%58.3%
Table 12. AGREE II Quality Assessment for Chemotherapy-Induced Peripheral Neuropathy and Cardiotoxicity Guidelines
AGREE II DomainCIPN (ONS)58aCIPN (NCCN)59bCardiotoxicity60aCardiotoxicity (ESMO)61a
  • AGREE II indicates Appraisal of Guidelines for Research and Evaluation II; CIPN, chemotherapy-induced peripheral neuropathy; ESMO, European Society for Medical Oncology; NCCN, National Comprehensive Cancer Network; ONS, Oncology Nursing Society.

  • a

    Guidelines rated by Cancer Guidelines Resource Centre.40

  • b

    Guidelines rated by M.L. McNeely and S.R. Harris.

Scope and purpose61.1%61.1%52.8%33.3%
Stakeholder involvement41.7%58.3%52.8%16.7%
Rigor of development46.9%27.1%29.2%16.7%
Clarity of presentation75.0%86.1%52.8%55.6%
Editorial independence20.8%79.2%25.0%12.5%
Table 13. AGREE II Quality Assessment for Bone Health Guidelines
  • AGREE II indicates Appraisal of Guidelines for Research and Evaluation II; ASCO, American Society of Clinical Oncology; NCCN, National Comprehensive Cancer Network.

  • a

    Guidelines rated by 2 authors (M.L. McNeely and S.R. Harris).

  • b

    Guidelines rated by Cancer Guidelines Resource Centre.40

Scope and purpose72.2%54.2%
Stakeholder involvement55.6%44.8%
Rigor of development26.0%42.3%
Clarity of presentation72.2%68.8%
Editorial independence79.2%33.3%


  1. Top of page
  2. Abstract
  6. Acknowledgements
  7. Note Added in Proof

Results will next be discussed based on each of the 3 objectives for this article. Syntheses of the guideline recommendations summarized in Tables 3 through 7 will be provided (Objective 1), followed by syntheses of the quality appraisal results presented in Tables 8 through 12 (Objective 2). Finally, recommendations for future evidence-based practice guidelines are presented (Objective 3).

Syntheses of Guideline Recommendations

Of the articles pertaining to lymphedema,29, 45-48 only 2 were true practice guidelines.45, 46 The older guideline45 differs from the prospective surveillance model (see Stout et al23) in recommending circumferential measurements for assessment and/or diagnosis of lymphedema in women at risk (Table 4); in the prospective surveillance model, volume measures are derived from circumferential measures taken every 5 mm. This latter recommendation is based on research published subsequent to the 2001 CPG, in which it was shown that volume measurements using an opto-electric volumeter were especially sensitive to subtle changes in upper limb volume.67 If an opto-electric volumeter (perometer) is available, albeit not common in clinical practice, it should be used in place of arm circumference measures. Another measure that shows promise in measuring early, fluid-based changes is bioimpedance spectroscopy, which is described in the Australian lymphedema guideline.46

As for interventions for lymphedema, there were consistent recommendations for the use of compression garments in the management of lymphedema,29, 45, 47 but only limited evidence to support compression bandaging in conjunction with manual lymph drainage (MLD) at the time these guidelines were published.45, 47, 48

Fortunately, there are a number of CPGs available on cancer-related pain, 6 of which were included in this review.49, 51-55 With regard to evaluation of pain, there was consistency across most of the guidelines that the patient's own report of pain intensity should be the primary source of assessment throughout initial and subsequent evaluations, that pain should be monitored regularly, and that visual analogue scales or other numerical rating scales should be used. Ongoing monitoring of pain is reflected also in the prospective surveillance model. There was also consistency across the guidelines that patients and their families should receive information and instruction about pain and take an active role in their own pain management, in conjunction with an interdisciplinary team approach. Nonpharmacologic interventions recommended for pain management included physical/occupational therapy, energy conservation strategies, transcutaneous electrical nerve stimulation, and acupuncture/acupressure.

Of the 2 cancer-related fatigue CPGs,56, 57 only the NCCN guideline56 included screening and evaluation recommendations, both of which are congruent with the prospective surveillance model. Both guidelines included recommendations for educating the patient about fatigue and the importance of activity enhancement or exercise as interventions to help manage fatigue,56, 57 elements that are also supported in the prospective surveillance model. As with the recommendations for pain management, an interdisciplinary team approach was encouraged in the NCCN guideline.56

The role of exercise and physical activity in helping to manage treatment-related peripheral neuropathy, cardiotoxicity, bone loss and/or fractures, and weight gain are just beginning to be recognized in some of the more recent CPGs (Table 8); additional, evidence-based recommendations should be incorporated into future guidelines in these areas as this evidence base continues to grow.

Methodological Quality of Guidelines

The upper extremity rehabilitation CPG and update43, 44 received strong appraisal scores (≥80%) in 3 of the 6 domains (Table 8). With regard to the lymphedema guidelines (Table 9), the Canadian Medical Association guideline45 received strong appraisal scores in 2 domains, as did the Ontario evidence summary.29, 47 The Australian CPG46 scored >80% in scope and purpose, whereas the highest domain score for the lymphedema PEP review48 was 63.9%.

Table 10 displays the AGREE II domain scores for guidelines on cancer-related pain.49-55 The Canadian Medical Association breast cancer pain guideline,49, 50 and the NCCN pain guideline51 received strong ratings only in clarity of presentation; all other ratings for the NCCN guideline were <50%. The Scottish Intercollegiate Guidelines Network (SIGN) pain guideline52 had the strongest ratings across all domains (all >80%), whereas the European Society of Medical Oncology53 guideline received the lowest overall domain ratings. The guideline by Cancer Care Ontario54 received strong scores in 3 domains. And, finally, the American Pain Society guideline55 scored ≥80% in just 1 domain: scope and purpose.

In Table 11, domain ratings for the 2 CPGs on cancer-related fatigue are provided.56, 57 Both guidelines were rated quite similarly for scope and purpose, stakeholder involvement, clarity of presentation, and editorial independence. Although the CPG from the Oncology Nursing Society (ONS) was rated more favorably in the third domain—rigor of development—the NCCN guideline was stronger in applicability (Domain 5).

Table 12 provides AGREE II ratings for the CIPN58, 59 and cardiotoxicity60, 61 guidelines. Of the 2 CIPN guidelines, only the NCCN guideline was rated ≥80%, and only in 1 domain. For the cardiotoxicity guidelines, all domain ratings were <60%. For the bone health guidelines62, 63 (Table 13), no domain was rated ≥80%.

Across the 9 guidelines rated by the authors, there was medium-level discordance in 4 domain appraisals (11.1% of all domains): stakeholder involvement (Domain 2) for the Cancer Care Ontario lymphedema evidence summary29, 46 and the Australian lymphedema guideline;48 and scope and purpose (Domain 1) and clarity of presentation (Domain 4) for the ONS fatigue guideline.57 Discrepant ratings in 2 domains in the ONS fatigue guideline57 likely arose because the information was not consolidated within the guideline chapter but appeared in a number of different places on the ONS Web site and various associated links, thus making it difficult to find.

For all 19 guidelines included in this review, Domains 3, 5, and 6 most frequently had the lowest ratings (eg, <30%): rigor of development (n = 6), applicability (n = 9), and editorial independence (n = 8). In contrast, ratings exceeded 80% for clarity of presentation (Domain 4) for nearly half (47.4%) of the guidelines.

Limitations of the AGREE II

In rating the CPGs not previously appraised, we struggled especially with assigning scores between 2 and 6, because there are no definitions for these scores.22 Another area of difficulty was Domain 6: Editorial Independence. Unless the criteria outlined in items 22 and 23 were explicitly stated in the guideline (or on the Web site), eg, a statement that the funding body did not influence the content of the guideline, description of any competing interests, and how they influenced the guideline process and recommendations, the item had to be scored as 1 (strongly disagree), even if the appraisers assumed that editorial independence existed based on the organization that had authored the guideline.

Another limitation of the AGREE II is that the focus on methodological issues related to guideline development and reporting is not sufficient to ensure that the recommendations themselves are “appropriate and valid.”22 In other words, as with most other guideline appraisal instruments, the greatest shortcoming of the AGREE (and subsequently the AGREE II) is their failure to assess “the quality of evidence” supporting the guideline's recommendations.21(p239) Whereas some guideline development organizations include expert opinion as an evidence source, others rely exclusively on randomized controlled trials (RCTs) and systematic reviews. The AGREE and AGREE II, similar to other guideline appraisal instruments, assess “the process of guideline development and how well it is reported”11(p69) but not the quality of evidence underlying the recommendations.

Recommendations for Updates and Future Evidence-Based Practice Guidelines

Although there are some excellent and recent CPGs in the areas of cancer-related pain and fatigue, most notably the SIGN guideline on pain,52 and regular updating of the guidelines is being done by both SIGN and NCCN, there is an urgent need for updated guidelines on the assessment and management of upper extremity musculoskeletal impairments and lymphedema. Since the development of these latter guidelines (between 2001 and 2008), a large body of published evidence, including RCTs and systematic reviews, has become available that would be critical in updating these guidelines.

For example, a 2007 systematic review68 and a more recent RCT69 have shown that resistance training is both safe and effective for women who have been treated for breast cancer. Another recent RCT has shown that early physical therapy (manual lymph drainage, scar tissue massage, active and active-assisted shoulder range of motion exercises) was effective in preventing lymphedema during the first year after surgery,70 and a 2011 meta-analysis reported a significant benefit of manual lymph drainage when added to compression therapy in treatment of breast cancer–related lymphedema.71 A 2010 Cochrane review reported that structured exercise during the postoperative period had significant short-term benefits in improving shoulder flexion range of motion, with physical therapy resulting in additional benefits for shoulder function.72 Certainly, the breadth and quality of research available since the upper extremity rehabilitation and lymphedema guidelines were published underscore the need for them to be updated and revised to incorporate this evidence.

Furthermore, additional research is needed to provide an evidence base for developing CPGs on the effects of exercise and/or physical therapy in the management of other impairments identified in the breast cancer prospective surveillance model, eg, arthralgia. The effects of physical rehabilitation interventions on patients' activity and life participation, as well as on their quality of life, also need to be studied so that CPGs can be developed in these important areas.


This review has summarized and synthesized recommendations from 19 CPGs relevant to breast cancer physical rehabilitation, published during the preceding decade. In addition, the guidelines were appraised using the AGREE II. Because of the scarcity of contemporary guidelines in 2 key areas—upper extremity impairment and lymphedema—as well as the availability of new and rigorous research in those areas, updated guidelines are urgently needed. The prospective surveillance model described in this supplement will provide an excellent framework within which to guide development of updated guidelines.

Fortunately, the recent and extremely comprehensive Institute of Medicine report, titled “Clinical Practice Guidelines We Can Trust,” includes specific steps for establishing evidence foundations for and rating the strength of guideline recommendations.11(pp124,125) The standards proposed within this report could assist greatly in ensuring that new guidelines are based on contemporary, rigorously designed empiric studies and independent processes for evidence retrieval, appraisal, and synthesis.11(pp75-144)


  1. Top of page
  2. Abstract
  6. Acknowledgements
  7. Note Added in Proof

The authors thank Ms. Charlotte Beck, health sciences reference librarian at the University of British Columbia, for her assistance in searching the literature for relevant clinical practice guidelines and Dr. Jane M. Armer of the Sinclair School of Nursing at the University of Missouri for her clarification of the evidence-based recommendations emanating from the Putting Evidence into Practice (PEP) card. And, finally, we are indebted to Ms. Kimberly S. Andrews, Research Associate in Cancer Control Science at the American Cancer Society, for her superb and patient editing of earlier drafts of this manuscript.

Note Added in Proof

  1. Top of page
  2. Abstract
  6. Acknowledgements
  7. Note Added in Proof


Support for this meeting and supplement were provided by the American Cancer Society through The Longaberger Company®, a direct selling company offering home products including handcrafted baskets made in Ohio, and the Longaberger Horizon of Hope® Campaign, which provided a grant to the American Cancer Society for breast cancer research and education.


The authors made no disclosure.


  1. Top of page
  2. Abstract
  6. Acknowledgements
  7. Note Added in Proof
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