A prospective model of care for breast cancer rehabilitation: Bone health and arthralgias§

Authors


  • The articles in this supplement were commissioned based on presentations and deliberations at a Roundtable Meeting on a Prospective Model of Care for Breast Cancer Rehabilitation, held February 24-25, 2011, at the American Cancer Society National Home Office, in Atlanta, Georgia.

  • The opinions or views expressed in this supplement are those of the authors, and do not necessarily reflect the opinions or recommendations of the editors or the American Cancer Society.

  • §

    A Prospective Surveillance Model for Rehabilitation for Women with Breast Cancer, Supplement to Cancer

  • Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms

Abstract

Musculoskeletal health can be compromised by breast cancer treatment. In particular, bone loss and arthralgias are prevalent side effects experienced by women treated with chemotherapy and/or adjuvant endocrine therapy. Bone loss leads to osteoporosis and related fractures, while arthralgias threaten quality of life and compliance to treatment. Because the processes that lead to these musculoskeletal problems are initiated when treatment begins, early identification of women who may be at higher risk of developing problems, routine monitoring of bone density and pain at certain stages of treatment, and prudent application of therapeutic interventions are key to preventing and/or minimizing musculoskeletal sequelae. Exercise may be a particularly suitable intervention strategy because of its potential to address a number of impairments; it may slow bone loss, appears to reduce joint pain in noncancer conditions, and improves other breast cancer outcomes. Research efforts continue in the areas of etiology, measurement, and treatment of bone loss and arthralgias. The purpose of this review is to provide an overview of the current knowledge on the management and treatment of bone loss and arthralgias in breast cancer survivors and to present a framework for rehabilitation care to preserve musculoskeletal health in women treated for breast cancer. Cancer 2012;. © 2012 American Cancer Society.

Breast cancer treatments can have broad adverse effects on the musculoskeletal system, including bone and muscle loss, arthralgias, and myalgias.1-6 Bone loss and arthralgias are particularly prevalent and can result from both chemotherapy and/or adjuvant endocrine therapy (Figure 1). Bone loss increases the risk of osteoporosis7, 8 and related fractures,9, 10 while arthralgias can impact quality of life and compliance with adjuvant endocrine therapy.11 Knowledge of the etiology, predictors, and potential treatments for arthralgias and bone loss can guide best practices for preventing and managing these musculoskeletal side effects, which commonly affect breast cancer survivors (BCSs). A particular emphasis on exercise as an intervention strategy will be given, because this single tool has potential to manage treatment-related musculoskeletal side effects as well as many other health problems facing BCSs.12

Figure 1.

Effect of breast cancer treatment on bone loss and development of arthralgias.

ARTHRALGIAS

Arthralgias are characterized by pain or stiffness in the joints,13 though swelling and structural changes are generally absent.11 Arthralgias are common in the general population, particularly in older women,14 and adversely influence quality of life and daily well-being.15 Loss of estrogen and vitamin D deficiency, high body mass index, and depression are frequent contributing factors.15, 16 Certain inflammatory disease states are also accompanied by generalized arthralgias, including autoimmune disorders such as fibromyalgia and several inflammatory conditions including osteoarthritis and inflammatory bowel disease.11 For peri- and postmenopausal women without these underlying disease states, arthralgias typically improve with hormone replacement therapy.14 Although the exact reason why hormone replacement therapy provides relief is unclear, synovial tissue contains estrogen receptors and estrogen can have an antinociceptive effect at the level of the joint or spinal cord.17-19 It is not surprising that types of breast cancer adjuvant endocrine therapy that result in actual or functional estrogen depletion are also associated with arthralgias. In addition, chemotherapy for breast cancer may contribute to joint symptoms.

Impact of Adjuvant Cancer Treatment

Arthralgias have been reported to occur in over 40% of women treated with chemotherapy,20 but they are more commonly associated with taxane-containing regimens.21 Because muscle and joint symptoms are often grouped together when reporting chemotherapy-related side effects, the incidence of arthralgias compared with that of other musculoskeletal symptoms is not always clear from large clinical trials.

Aromatase inhibitors (AIs) are currently the adjuvant and first-line systemic endocrine treatment of choice for postmenopausal women with estrogen receptor–positive tumors.22 Up to 50% of women taking AIs report arthralgias.13, 23-28 AI-related arthralgias appear to be more frequent or severe in women who had chemotherapy, are within 5 years of menopause at treatment initiation, used hormone replacement therapy before diagnosis, are obese, and/or have a specific genetic profile.2, 29, 30 Several mechanisms have been proposed to explain the association between the use of AIs and arthralgias,1, 31 including those related to low estrogen,17-19 fluid retention in the joint, and increased systemic inflammation, though evidence for the latter remains unconvincing. Although the clinical picture for AI-related arthralgias is variable, it usually includes onset of stiffness and pain within 1-2 months in bilateral and multiple joints, including the hands, shoulders, lower back, hip, knees, and feet.11 The stiffness and discomfort is often greatest upon awakening and improves with movement during the day. The clinical course is variable, and many patients with mild arthralgias may report a lessening of symptoms after several months, whereas others continue to have symptoms until the AI is stopped. In addition to pain and stiffness, clinical syndromes of trigger finger and carpal tunnel syndrome have been reported.32, 33 Joint discomfort and stiffness is an important underlying cause of nonadherence and early discontinuation of AI treatment.34 Reported discontinuation rates for AIs are as high as 40% at 2 years34 and 50% at 5 years.35

The selective estrogen receptor modulator tamoxifen is considered a first-line adjuvant endocrine therapy for premenopausal women with breast cancer.22 Arthralgias have been reported in up to 10% of women on tamoxifen, particularly for women on the generic version of the drug.13, 26, 36 It is unclear whether the incidence of arthralgias with tamoxifen is significantly different than that with placebo37, 38; however, switching from generic tamoxifen to Novladex36 has been reported to alleviate most cases of tamoxifen-related arthralgias.

Measurement of Arthralgias in Patients with Breast Cancer

There is an elevated background level of joint pain and symptoms in the peri- and postmenopausal female population, which points to the need for early evaluation of arthralgias in the breast cancer setting.39 In large clinical treatment trials focused on cancer end points, arthalgias are usually recorded as an adverse event using the Common Toxicity Criteria of the National Cancer Institute (Version 2), which may result in underreporting of athralgia symptoms. Intervention studies to improve arthralgias in BCSs typically use the Brief Pain Inventory40 to document arthralgias.41-43 Measurement tools from the arthritis or rehabilitation literature have also been used in BCSs42 to capture joint symptoms at the knee, such as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC),44 and hands, such as the Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH).45 Furthermore, the Disabilities of the Arm, Shoulder and Hand (DASH) or shorter Quick DASH,46 designed to measure pain-related upper quadrant function, symptoms, and disability, has been used with BCSs in relation to surgery or lymphedema.47 The applicability of these symptom assessment tools in the breast cancer setting has not been established. Grip strength is increasingly used to evaluate the efficacy of interventions to reduce AI-related arthralgais based on observations that grip strength is lower in individuals with AI-related musculoskeletal symptoms.48 In the absence of a gold standard method for assessing arthralgias in BCSs, it is important that clinicians determine if breast cancer patients are experiencing arthralgias and track them using any one or several of the above methods. Instruments that measure multiple constructs (ie, symptoms and function) may be preferable to tools focused on a single one.

Population-based studies involving representative samples of BCSs and using standardized measurement tools are clearly needed to develop a better understanding of the prevalence of arthralgias in BCSs. Such studies can also determine the characteristics that predict which women are more susceptible to developing arthralgias. Development, validation, and adoption of an instrument to specifically capture AI-related arthralgias in BCSs would vastly improve the quality of surveillance and intervention efforts.

Current Strategies for Management of Cancer-Treatment Related Arthralgias

At present, there are no clinical guidelines for the prevention and treatment of arthralgias in BCSs. We review recommendations on potential management strategies from the literature.49-54 First, it is important to educate women on AIs experiencing primarily morning stiffness that their symptoms are likely to improve throughout the day as activity levels increase. Second, it is important to ensure adequate vitamin D levels among BCSs experiencing arthralgias. Several preliminary studies suggest that vitamin D supplementation in women who are vitamin D–insufficient or –deficient may prevent or reduce joint pain in BCSs on AIs.55-57 Until the target level of serum 25 hydroxyvitamin D (25 OHD)—which might be needed to reduce AI-related arthralgias—is determined, the general population serum 25 OHD target of 20-50 ng/mL and dietary intake targets of 600 IU/d for adults 19-70 years and 800 IU/d for adults >70 years should be followed.58 Switching to a different AI is sometimes effective in reducing symptoms so that women can remain on treatment.59 Additionally, a small placebo-controlled trial has suggested that acupuncture may be effective in reducing AI-related arthralgias.42 There is little evidence that anti-inflammatory drugs are effective in relieving AI-related arthralgias in BCSs.52, 53 When pain is severe or interferes with activity and is unresolved with above measures, or if clinical symptoms of carpal tunnel syndrome or trigger finger appear, discontinuation of the AI or switching to another endocrine therapy (such as tamoxifen) may be recommended.

General recommendations for arthralgias not associated with AI use include exercise, weight loss when appropriate, and nonsteroidal anti-inflammatory agents as needed.49-54, 60 Exercise is included in standard recommendations for reducing joint pain related to conditions other than cancer65; however, at this time, there is no research to suggest that exercise can alleviate AI-related arthralgias. There are not yet any published controlled trials investigating exercise to reduce AI-related arthralgias, but trials are underway. Until an evidence base is formed about exercise safety and efficacy for AI-related arthralgias, health care providers should actively monitor patients to evaluate any pain-relieving benefit from exercise. If exercise exacerbates arthralgias, selecting an alternative mode or reducing exercise volume may relieve symptoms so that patients can maintain an active lifestyle in spite of pain. Concurrent conditions, including excess weight and poor sleep quality, may result from and/or exacerbate AI-related arthralgias; therefore, exercise could provide some pain relief through weight loss61 and can also promote better sleep.62

BONE HEALTH

In the last decade, the side effects of cancer treatment on the skeleton have become well recognized1, 3, 4 (Figure 1), and concerns about elevated fracture risk in BCSs have been raised.63, 64 Risk factors for osteoporosis and related fractures have been identified (Table 1) and are used in screening and treatment recommendations in the general population (www.nof.org). These same risk factors apply to BCSs,63, 65, 66 but cancer treatment causes additional bone loss that could increase the risk of osteoporosis and related fractures above that in cancer-free women. Chen et al7 reported significantly lower hip bone mineral density (BMD) and a greater prevalence of osteoporosis at any skeletal site (27%) among postmenopausal BCSs aged 50-79 years (n = 209), compared with cancer-free women (19%; n = 5759). The Cancer and Menopause Study (CAMS) of women aged 50 years or younger at breast cancer diagnosis identified lower Z-scores, indicating below-age-expected BMD, at the spine among BCSs who were postmenopausal at dual energy x-ray absorptiometry (DXA) evaluation and who had received chemotherapy independent of adjuvant tamoxifen use.67 Smaller studies have reported greater rates of osteopenia at the spine and hip in BCSs compared with age-based norms68 or cancer-free controls,66 with a single conflicting report that BMD is no worse and possibly better among BCSs (n = 80) than in matched cancer-free controls.69

Table 1. Risk Factors of Osteoporosis and Related Factures in the General Female Population and Additional Risk Factors for Women Treated for Breast Cancer
General Female PopulationBreast Cancer Survivors
• Low body weight• Adjuvant chemotherapy
• Advanced age • Positive family history of osteoporosis • Caucasian or Asian race • Low estrogen due to menopause (natural, surgical) • Abnormal absence of menstrual periods (amenorrhea) • Medications, such as corticosteroids and anticonvulsants • Low dietary calcium and vitamin D • Sedentary lifestyle • Cigarette smoking • Excessive use of alcohol • Propensity to fall • Previous nontraumatic (or fragility) fracture• Chemotherapy-induced ovarian failure or ovarian suppression • Tamoxifen, if premenopausal • Aromatase inhibitors

The clinical consequence of osteoporosis is a fracture, with hip fractures having the greatest impact on morbidity and mortality.70, 71 In the largest report to date using data from the Women's Health Initiative (WHI) study (n = 146,959), Chen et al72 reported a significantly elevated hazard ratio of hip fracture of 1.55 (95% confidence interval [CI], 1.13-2.11) in women with incident breast cancer and a nonsignificant increase in risk of vertebral fracture of 1.26 (95% CI, 0.94-1.69). Annualized rates of fractures were similar between BCSs prior to cancer diagnosis and controls, suggesting that the increase in fracture risk among BCSs was disease and/or treatment related.

Impact of Chemotherapy

Women who are premenopausal at breast cancer diagnosis and who subsequently develop chemotherapy-induced ovarian failure face significant and abrupt bone loss from estrogen deprivation. Ovarian failure affects approximately 70% of premenopausal women over 40 and 40% of younger women.73, 74 Annual rates of bone loss in women who become menopausal during treatment average 3%-8% at the spine and 4%-5% at the hip75-78 compared with losses of 2%-4% resulting from natural menopause.78, 79 Administration of gonadotropin-releasing hormone (GnRH) agonists to suppress ovarian function in premenopausal breast cancer patients results in similar bone loss as that from chemotherapy-induced ovarian failure.80 Return of ovarian function following cessation of GnRH treatment can lead to some recovery of BMD. For example, after 2 years of goserelin therapy, BMD at the hip and spine increased in a subsequent off-treatment year by 2% and 4%, respectively, though recovery values remained significantly below pretreatment levels.80

Though estrogen deprivation has the strongest impact on bone health, chemotherapy alone can contribute to bone loss even in postmenopausal women.81-84 Women who are postmenopausal at the time of breast cancer diagnosis still experience bone loss across the course of chemotherapy,81, 85 as do breast cancer patients who never lose ovarian function during chemotherapy treatment.83 Chemotherapy-induced bone loss may result from the direct effects of cytotoxic drugs on bone cell number and function84, 86, 87 and/or decreased physical activity.88

Impact of Adjuvant Endocrine Therapy

Whether tamoxifen has agonist or antagonist effects on bone density depends on the estrogen environment. In postmenopausal women, tamoxifen can reduce or prevent bone loss,89-93 but it accelerates loss in premenopausal women with intact ovarian function.94 AI treatment in postmenopausal women results in profound estrogen depletion and is associated with greater bone loss and a 2- to 3-fold higher risk of fractures when compared with postmenopausal women receiving tamoxifen.95-97 Annual rates of bone loss from AI treatment range from 3%-4% at the spine and 1%-2% at the hip.4 Whether long-term AI use significantly increases fracture risk compared with placebo remains unclear.3 However, a 3-year trial of exemestane versus placebo to prevent breast cancer in postmenopausal women reported no significant increase in fractures.98

Evaluating Bone Health in Breast Cancer Patients

The current gold standard for osteoporosis evaluation is measurement of bone mineral density (BMD; g/cm2) via DXA. BMD is inversely related to bone fragility and fracture risk.99 As site-specific BMD yields the best indication of fracture risk of a particular skeletal region, BMD should be measured at the hip and spine: fracture sites with the greatest morbidity and mortality rates.100-102 When measurement at the hip or spine is not possible, forearm BMD assessment can be used for diagnosis.103 DXA precision error is quite low (coefficient of variation <1.0%-1.5%), making it an ideal tool to evaluate treatment efficacy and/or strategies designed to alter bone density. Due to its high rate of turnover, the spine is a particularly sensitive region for monitoring bone changes.104 Although BMD remains the most widely used clinical tool for assessing fracture risk and indicating treatment, it is not a perfect predictor of fractures.105 To expand the predictive ability of DXA and incorporate additional clinical factors to predict fracture risk, particularly for women who have nonosteoporotic DXA T-scores, the World Health Organization developed a country-specific fracture risk index (FRAX) that estimates 10-year probabilities of hip and major osteoporotic fracture.106 FRAX scores are calculated from an algorithm that incorporates femoral neck T-score (if known), age, body mass index, fracture history, smoking, glucocorticoid use, alcohol consumption, and presence of rheumatoid arthritis. Though gaining use in primary care practice,106 the additional predictive validity of FRAX beyond BMD is uncertain,107, 108 and because cancer-specific information was not considered in the model, its use in BCS populations needs further study.

While DXA remains the current gold standard for assessing fracture risk, other approaches are of interest because they may overcome some of the limitations of DXA. Because bone strength is a function of both bone mass and bone architecture, three-dimensional imaging techniques that capture bone geometry, a known limitation of DXA, could improve fracture prediction. Alterations in bone geometry indices are associated with fractures in postmenopausal women.109 Quantitative computed tomography (QCT) measures both volumetric bone density (g/cm3) and architecture at the hip and spine using conventional body CT scanners or at the radius and tibia. Although BMD measured by QCT is more precise than DXA, World Health Organization osteoporosis criteria using T-scores cannot be applied to QCT-derived data. Currently, QCT is not recommended for fracture prediction due to insufficient evidence that it is superior to DXA.110

A less sensitive and specific yet convenient and popular technique because of its convenience in screening situations is quantitative ultrasound (QUS). QUS is based on the principles of ultrasound, where a sonographic pulse that is transmitted across the heel is attenuated in proportion to the number and quality of trabeculae within the calcaneus. Bone integrity is measured by both broadband ultrasound attenuation (dB/MHz) and speed of sound (m/s); both measures are reduced in osteoporotic patients.111 The inability to apply T-scores using a peripheral site and the poor reliability of day-to-day QUS prohibit its use as a tool for monitoring therapeutic or time-related bone changes.112 QUS should be restricted to use as a screening tool with recommendations for central DXA evaluation when indicated.

Bone turnover, as evidenced by biomarkers of both bone formation and resorption, can predict fracture independent of BMD and may assess microarchitectural integrity of bone.113 Bone turnover is significantly elevated in response to chemotherapy-induced ovarian failure77 and AI treatment,96, 114 but decreased in response to tamoxifen.114 There are several markers of bone turnover, with the cross-linked telopeptide of type I collagen, showing the most promise as a monitoring tool.113 Individuals with both low BMD and high levels of biomarkers of turnover (above premenopausal norms) should be considered at higher risk of fracture than those with either condition alone.115 The use of biomarkers to monitor responsiveness to therapeutic interventions or predict fracture risk in BCSs has not yet been established.

Current Clinical Guidelines for Prevention and Treatment of Cancer Treatment–Induced Bone Loss

Both the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) have issued guidelines for the identification, monitoring, and management of bone health in BCSs (Table 2).64, 116 The ASCO follows the US Preventive Service Task Force clinical guidelines recommending BMD screening and monitoring,117 which includes positive lifestyle behaviors such as adequate calcium and vitamin D for all women, and medication management for women with osteoporosis. The ASCO guidelines do not currently endorse bisphosphonate use in the absence of bone metastases. A recent update to the NCCN Clinical Practice Guidelines in Oncology for Breast Cancer and Prostate Cancer (www.nccn.org) recommends that patients whose cancer treatment aims to lower sex steroids should have a baseline BMD assessment and that the FRAX algorithm be applied.64 Regular BMD monitoring and lifestyle adjustments are recommended for all women, and slightly more conservative than the ASCO guidelines, the NCCN urges that therapeutic intervention be considered when BMD T-score falls at or below -2.0, particularly when additional risk factors are evident. Hadji et al118 provides an algorithm similar to that of the NCCN, but is specific to postmenopausal BCSs on adjuvant AI treatment, recommends bisphosphonates at a higher T-score in at-risk women, and takes into consideration the use of intravenous bisphosphonate therapy when implicated. Although osteonecrosis of the jaw associated with intravenous bisphopshonates is considered uncommon among women with AI-associated bone loss, regular attention to dental care and oral health are prudent during therapy.118

Table 2. Current Clinical Management Guidelines of Cancer Treatment–Induced Bone Loss in Breast Cancer Survivors
 ScreeningAssessmentTreatment
All WomenPharmacological Treatment Criteria
  1. Abbreviations: AI, aromatase inhibitor; ASCO, American Society of Clinical Oncology; BMD, bone mineral density; DXA, dual energy x-ray absorptiometry; FRAX, fracture risk index; NCCN, National Comprehensive Cancer Network.

ASCOBMD screening for all women >65 y Women 60-64 y with any of following:Annual DXA unless considered low-riskAdequate calcium (1200 mg/d) and vitamin D (400-800 IU/d) intakeBMD T-score ≤−2.5
• Family history of fracturesPhysical activityPrior fragility fracture
•Body weight <70 kgSmoking cessation
•Prior nontraumatic fracture
•AI use
•Premature ovarian failure
NCCNBaseline BMD and FRAX algorithm for any patient on cancer therapy that includes the following:Biannual DXA in patients receiving treatments known to cause bone lossAdequate calcium (1200 mg/d) and vitamin D intake (800-1000 IU/d)BMD T-score ≤−2.0
•Premature ovarian failureAnnual DXA if accelerated bone  loss is suspected or therapeutic intervention appliedPhysical activity
•Adjuvant hormone therapy that reduces estrogen or interferes with estrogen actionSmoking cessation
•GlucocorticoidsLimiting alcohol use
Hadji et al118BMD screening and risk factor assessment for women planned to receive or receiving treatment with AIDXA and risk status every 1-2 y for all patientsAdequate calcium (1300 mg/d) and vitamin D intake (600 IU/d)BMD T-score ≤−2.0 or 2 of any of the following risk factors
Individually monitored BMD for patients on oral bisphosphonatePhysical activity • T-score ≤−1.5
 • Age >65 y
• Low BMD (<20 kg/m2)
• Family history of hip fracture
• Personal history of fragility fracture at >50 y
• Oral corticosteroid use for >6 mo
• Smoking (current and past)

Exercise for Prevention and Treatment of Bone Loss in BCSs

Clinical management guidelines to address bone health in cancer survivors focuses largely on screening and pharmacologic treatment.64, 116 Although specific recommendations for calcium and vitamin D are provided, no target prescription is given for physical activity, despite existing knowledge about bone-loading exercise.119-123 The American College of Sports Medicine (ACSM) position on exercise and bone health outlines evidence-based recommendations for promoting bone health across the lifespan for the general population (Table 3),119 which is not addressed by the ACSM Roundtable Exercise Guidelines for cancer survivors.12 Work is currently underway to better understand the efficacy of exercise as a therapeutic intervention for cancer-related bone loss, the optimal and safe effective dose of exercise to prevent bone loss and how exercise compares with or acts with bisphosphonates.124 Only 2 trials have evaluated whether exercise can prevent anticipated bone loss from breast cancer treatment. Schwartz et al125 compared effects of moderate intensity aerobic (mixed modes) training or resistance training using exercise bands versus usual care on spine BMD in women receiving chemotherapy for breast or other cancers. Compared with BMD loss of 6.7% for women given usual care, aerobic trained women nearly maintained (−0.76%) BMD at the spine and the difference in BMD was statistically significant between these groups. Resistance training did not prevent bone loss at the spine; however, the use of resistance bands may have made it difficult to achieve an intensity necessary to stimulate bone adaptation,126, 127 and the exercises targeted the whole body, rather than musculature attached to the spine.128 Swenson et al129 reported that a daily walking program did not prevent bone loss nor elevations in bone turnover in premenopausal and newly postmenopausal BCSs initiating chemotherapy, whereas oral bisphosphonate therapy stabilized bone outcomes. The high walking levels among participants at baseline in this study combined with the low osteogenic potential of walking as a bone loading exercise121 suggests that an inadequate stimulus may have been applied.

Table 3. American College of Sports Medicine Exercise Guidelines to Preserve Bone Health During Adulthood in the General Female Population
ModeWeight-bearing endurance activities (tennis; stair climbing; jogging, at least intermittently during walking)
Activities that involve jumping (volleyball; basketball) Resistance exercise targeting all major muscle groups
IntensityModerate to high in terms of bone-loading forces (ie, ground reaction forces >2 times body weight)
Duration30-60 min/d of a combination of weight-bearing endurance activities, activities that involve jumping, and resistance exercise
FrequencyWeight-bearing endurance activities 3-5 times per week
Resistance exercise 2-3 times per week

Other randomized controlled trials have evaluated the efficacy of either aerobic130, 131 or resistance exercise132, 133 to restore bone health after treatment and prevent further loss. One year of mixed-mode, moderate intensity aerobic training preserved total body BMD among posttreatment, postmenopausal BCSs compared with a 1.7% loss in controls.130 In contrast, Rogers et al131 did not report any effect of short (3-month) home-based walking program on hip or spine BMD measured 3 months later in pre- and postmenopausal BCSs on adjuvant hormone therapy. Winters-Stone et al133 reported preservation of spine BMD (+0.5%) with 12 months of moderate-vigorous intensity resistance and impact training compared with BMD losses (−2.1%) in a stretching control group in postmenopausal BCSs 1 year out from radiation or chemotherapy. Differences at the spine were similar across adjuvant hormone therapy groups (none, selective estrogen receptor modulator, AI). The addition of low-to-moderate intensity resistance training to bisphosphonate therapy improved hip and spine BMD and reduced turnover slightly, but not significantly more than bisphosphonate alone among a large cohort (n = 249) of postmenopausal, posttreatment BCSs.132

Based on a very limited number of trials, moderate-intensity exercise may preserve bone health during or after cancer treatment. Because neither of the studies comparing exercise to bisphosphonates included a group that did not receive medication, whether exercise had some benefits to bone health compared with no treatment at all remains unclear. For all women, including those who may begin or are on bisphosphonate therapy, adequate dietary calcium and vitamin D intake and regular participation in weight-bearing exercise are the foundation for skeletal health and reducing fracture risk.64, 103, 116 Consistent with general recommendations for preserving bone health in the general population,119 aerobic, resistance, and impact training performed at moderate-high intensities preserves spine BMD in BCSs. Additional study and design of programs to specifically improve BMD at the hip in BCSs are warranted, because hip fractures are elevated among BCSs10 and are associated with poor health outcomes.70 Meta-analyses of exercise training studies in women without cancer suggest that mixed-mode aerobic training or resistance training is beneficial at this skeletal site.122, 123, 134-137 In the absence of sufficient evidence for an exercise prescription to prevent or treat bone loss specifically in BCSs, the ACSM exercise recommendations to preserve bone health in the general population should be applied.119 Since falls are a major contributor to fractures138 and BCSs may be at greater risk of falls,10, 66, 139 fall prevention exercise programs140 should also be promoted, though the efficacy of these programs to prevent falls in BCSs remains to be determined.

Surveillance Model for Physical Rehabilitation for Arthralgias and Bone Loss in BCSs

Early identification of BCSs at risk for bone loss and/or arthralgias and screening for presence of low bone mass and joint pain are key to initiating early interventions that could minimize musculoskeletal symptoms and side effects (Table 4). Because both problems are associated with chemotherapy and/or adjuvant hormone therapy, BMD and arthralgia assessments prior to commencing these treatments and annually thereafter are recommended. Screening should be done more frequently when symptoms arise, when medical status changes, or as new treatments are applied that alter risk factors. These assessments can identify individuals at risk, determine the impact of treatment, monitor therapeutic interventions, and determine when medication management may be necessary. An individualized exercise program should be prescribed as early as possible and preferably before adjuvant treatment begins so that the severity of musculoskeletal side effects may be minimized. Even low-intensity exercise could lower fall risk141 and preserve function12 during treatment. Patients could progress to more vigorous exercise as tolerated, which may provide stronger bone benefits for those at risk of fracture.

Table 4. Surveillance Model for Physical Rehabilitation for Arthralgias and Bone Loss in Breast Cancer Survivors
Breast Cancer Diagnosis and Treatment Planning (Preoperative Rehabilitation Evaluation)Postoperative Period (Early Postoperative Rehabilitation)Adjuvant Treatment and Survivorship Care (Ongoing Rehabilitation Surveillance)
  • Abbreviations: AI, aromatase inhibitor; BMD, bone mineral density; DXA, dual energy x-ray absorptiometry.

  • a

    If <1 year from prior DXA, do not repeat but use most recent DXA as baseline.

Arthralgias  
Identify patients who may already be at risk for arthralgias and/or become at risk due to any of the following: Conduct baseline assessment of arthralgias in patients planned to begin AI therapy
• Postmenopausal• Repeat yearly or based on symptoms
• Excess body weight
Plan for future assessment of risk and patient educationProvide patient education about arthralgias for patients planned to begin AI therapy
Bone loss  
Identify patients who may already be at risk for bone loss and/or become at risk due to any of the following:Conduct baseline assessment of BMD (via DXA) for at-risk patientsTake and/or repeat assessment of BMD (via DXA) prior to adjuvant interventiona
• Age >65 yearsProvide education based on risk factors for osteoporosis and fractures
• Age <65 years with risk factors for osteoporosis
• Age >40 years and likely to receive adjuvant chemotherapy
Plan for postoperative assessment of risk, patient education, and activity prescriptionInitiate and/or resume exercise program emphasizing fracture risk reduction
• Evaluation of activity limitations
• Individualized exercise prescription
• Referral to appropriate exercise program if needed

FUNDING SOURCES

Support for this meeting and supplement was 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.

CONFLICT OF INTEREST

The authors made no disclosures.

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