Feasibility and promise of a 6-week program to encourage physical activity and reduce joint symptoms among elderly breast cancer survivors on aromatase inhibitor therapy
Introduction
Breast cancer is the most common cancer among women in the U.S., with estimated 232,340 new diagnoses in 2013 and a lifetime risk among women born today of 1 in 8.1 Most new diagnoses are made in postmenopausal women, generally at an early and curable stage, with hormone receptor positive (HR +) tumors, and where there is a significant survival benefit from adjuvant endocrine therapy.[2], [3], [4], [5] For such patients, the American Society of Clinical Oncology Clinical Practice Guideline: Update on Adjuvant Endocrine Therapy for Women with Hormone Receptor-Positive Breast Cancer and the International Society of Geriatric Oncology recommend that adjuvant endocrine therapy include a third generation aromatase inhibitor (AI) – anastrozole, exemestane, or letrozole – as part of treatment.[6], [7]
Non-inflammatory joint pain, stiffness or achiness – known as AI-associated arthralgia (AIA) – is a common and troublesome side-effect.[8], [9], [10], [11] In clinical trials, estimates of AIA range from 5% to 36%[12], [13], [14], [15]; however, reporting of musculoskeletal events was inconsistent in these trials and did not include patient-reported symptom questionnaires inquiring specifically about musculoskeletal symptoms.[9], [16] In clinical practice, by contrast, estimates of adverse joint symptoms are estimated as high as 33% to 74% among patients on AI therapy.[17], [18], [19], [20], [21], [22], [23], [24] Of those who report AIA, almost 70% rate their symptoms as moderate to severe.[18], [21] Sites most often affected include knees, feet, pelvic and hip bones, back, hands (fingers, wrists), and arms.[16], [23], [25] Symptoms can appear anywhere from 6 weeks to 12 months of starting AI therapy, increase over time, cease upon discontinuation of AI therapy, and range from minor to moderate or severe.[18], [26], [27]
For survivors whose symptoms are moderate to severe, there are growing concerns that AIA can undermine full adherence with doctor-recommended AI dosage[17], [18], [23], [28], [29] and thereby compromise treatment efficacy.[3], [28], [30] Complete discontinuation due to side-effects ranges from 20% to 32%.[18], [23], [31], [32] Both self-medication at lower-than-recommended doses and complete discontinuation of AI due to side effects are important survivorship concerns for oncologists treating patients with breast cancer.[28], [33] Switching among AIs is a common AIA management option,[34], [35] and pharmaceutical treatment options include analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), pain modifiers, and sleep aids.[3], [8], [10], [36], [37] However, to date, there have been no formal assessments of these symptom management options in clinical trials.[3], [9] More importantly, for too many survivors on AI therapy, pharmacological remedies provide little or no relief18 and have their own adverse side effects.38 There is a need for effective, easy-to-use, and sustainable adjunctive approaches to AIA management,30 to minimize or ameliorate symptoms so that survivors remain on AI therapy to maximize breast cancer specific survival.
We conducted a pilot study to investigate whether a scalable (easy to implement) physical activity intervention – a self-directed walking program – is feasible and potentially effective in providing relief for survivors on AI therapy who report joint pain or other joint symptoms. The general benefits of physical activity for overall survival, quality of life and cardiovascular health are already well-established through randomized controlled trials (RCTs) and observational studies conducted over the past several decades[39], [40], [41], [42], [43], [44], [45], [46]; in fact, guidelines encourage persons diagnosed with cancer to participate in physical activity.[47], [48], [49] The physical activity intervention evaluated in this pilot study – the Arthritis Foundation's self-directed walk with ease (WWE) program – is evidence-based for reducing self-reported arthritis or joint pain among adults. The primary outcomes of interest are the feasibility of (a) recruiting and retaining our target population for the intervention study and2 increasing walking among study participants during the 6-week WWE program. Secondary outcomes of interest were preliminary evidence of positive program impacts (promise) on patient-reported outcome measures related to joint pain, stiffness and fatigue and self-efficacy to manage joint symptoms.
Section snippets
Setting and Participants
Target enrollment was 20 breast cancer survivors. Participants were recruited on a consecutive basis between June and October 2012 through breast cancer clinics at the North Carolina Cancer Hospital (NCCH). The study team identified potential participants – female breast cancer survivors age 65 or older and on AI therapy for three months or more – through a review of medical records of patients scheduled for an NCCH clinic visit. For each potential participant identified through this process,
Results
A review of medical records for scheduled patients identified 61 potential participants—female patients with breast cancer, age 65 or older on AI therapy for 3 months or more. Treating clinicians determined that: (a) 7 patients (11%) had medical conditions that were too complex for a physical activity program, (b) 10 patients (16%) were not AI compliant (stopped or never started), and (c) 13 patients (21%) were not experiencing joint pain. Of the remaining 31 patients approached by the study
Discussion
The purpose of our pilot study was to investigate whether a self-directed walking program was feasible and potentially effective in providing relief for elderly breast cancer survivors on AI therapy who report joint pain or other joint symptoms. Our findings show that a self-directed walking program is feasible from two perspectives. First, it is feasible to identify and recruit study participants by working collaboratively with breast cancer oncologists and nursing staff in a busy clinic
Disclosures and Conflict of Interest Statements
There is no conflict of interest.
Author Contributions
Study concepts and design: L.F. Callahan, H.B. Muss, K.A. Nyrop, M. Altpeter
Data acquisition: K.A. Nyrop, B. Hackney
Data analysis and interpretation: K.A. Nyrop, R. Cleveland
Manuscript preparation: K.A. Nyrop
Manuscript editing and review: L.F. Callahan, H.B. Muss, K.A. Nyrop, M. Altpeter
Final approval of manuscript: All authors
References (81)
- et al.
Special issues related to breast cancer adjuvant therapy in older women
Breast
(2005) - et al.
Management of breast cancer in elderly individuals: recommendations of the International Society of Geriatric Oncology
Lancet Oncol
(2007) - et al.
Aromatase inhibitor-induced arthralgia: clinical experience and treatment recommendations
Cancer Treat Rev
(2008) - et al.
Aromatase inhibitor-associated arthralgia and/or bone pain: frequency and characterization in non-clinical trial patients
Clin Breast Cancer
(2007) - et al.
Tolerance of adjuvant letrozole outside of clinical trials
Breast
(2008) - et al.
Current opinion of aromatase inhibitor-induced arthralgia in breast cancer in the UK
Clin Oncol
(2011) - et al.
Side effects of aromatase inhibitors versus tamoxifen: the patients' perspective
Am J Surg
(2006) Assessment of chronic pain I. Aspects of the reliability and validity of the visual analogue scale
Pain
(1983)The validity and reliability of pain measures in adults with cancer
J Pain
(2003)- et al.
Cancer pain assessment in clinical trials
J Pain Symptom Manage
(2005)
Quality of life issues in relation to the aromatase inhibitor
J Steroid Biochem Mol Biol
Breast cancer: SEER fact sheets. National Cancer Institute [Internet]
Adjuvant therapy for older women with breast cancer
Cancer J
Aromatase inhibitor therapy: toxicities and management strategies in the treatment of postmenopausal women with hormone-sensitive early breast cancer
Breast Cancer Res Treat
Adjuvant treatment of elderly breast cancer patients
Breast
American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer
J Clin Oncol
Musculoskeletal adverse events associated with adjuvant aromatase inhibitors
J Oncol
Management of arthralgias associated with aromatase inhibitor therapy
Curr Oncol
Aromatase inhibitor-associated musculoskeletal symptoms: etiology and strategies for management
Oncology (Williston Park)
Results of the ATAC (arimidex, tamoxifen, alone or in combination) trial after completion of 5 years' adjuvant treatment for breast cancer
Lancet
A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer
N Engl J Med
A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer
N Engl J Med
A randomized controlled trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer
N Engl J Med
Aromatase inhibitor-associated arthralgia syndrome
Breast
Arthralgia during aromatase inhibitor treatment in early breast cancer
Cancer Nurs
Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer
J Clin Oncol
Sonographic and electrodiagnostic evaluations in patients with aromatase inhibitor-related arthralgia
J Clin Oncol
Functional disability and aromatase inhibitor-associated arthralgia in breast cancer survivors
J Clin Oncol
Patterns and risk factors associated with aromatase inhibitor-related arthralgia among breast cancer survivors
Cancer
Is the toxicity of adjuvant aromatase inhibitor therapy underestimated? Complementary information from patient-reported outcomes (PROs)
Breast Cancer Res Treat
The time since last menstrual period is important as a clinical predictor of non-steroidal araomatase inhibitor-related arthralgia
BMC Cancer
Aromatase inhibitors and arthralgias: a new frontier in symptom management for breast cancer survivors
J Clin Oncol
Aromatase inhibitors and arthralgia
J Clin Oncol
Defining aromatase inhibitor musculoskeletal symptom: a prospective study
Arthritis Care Res
Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer
Breast Cancer Res Treat
Adherence to initial adjuvant anastrozole therapy among women with early-stage breast cancer
J Clin Oncol
Aromatase inhibitor-induced arthralgia in early breast cancer: what do we know and how can we find out?
Breast Cancer Res Treat
Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer
J Clin Oncol
Effect of a switch of aromatase inhibitors on musculoskeletal symptoms in postmenopausal women with hormone-receptor positive breast cancer: the ATOLL (articular tolerance of letrozole) study
Breast Cancer Res Treat
Therapeutic optimization of aromatase inhibitor-associated arthralgia: etiology, onset, resolution, and symptom management in early breast cancer
Community Oncol
Cited by (37)
Study design and methods for the using exercise to relieve joint pain and improve AI adherence in older breast cancer survivors (REJOIN) trial
2021, Journal of Geriatric OncologyCitation Excerpt :Increasingly, non-pharmacological approaches are needed to provide safe, long-term relief to help survivors cope with treatment side effects [32]. The Using Exercise to Relieve Joint Pain and Improve AI Adherence in Older Breast Cancer Survivors (REJOIN) trial builds on previous trials seeking to address arthralgia and AI adherence through education-only [33,34] or exercise-only programs [35,36]. Programs combining education and exercise are key, but previous studies have not been tailored to older BCS [31,37].
Trans sectoral care of geriatric cancer patients based on comprehensive geriatric assessment and patient-reported quality of life - Results of a multicenter study to develop and pilot test a patient-centered interdisciplinary care concept for geriatric oncology patients (PIVOG)
2017, Journal of Geriatric OncologyManagement of aromatase inhibitor induced musculoskeletal symptoms in postmenopausal early Breast cancer: A systematic review and meta-analysis
2017, Critical Reviews in Oncology/HematologyCitation Excerpt :Three studies investigated a combined aerobic and resistance exercise program, including two randomised control trials (Irwin et al., 2015; Lohrisch et al., 2011), and one pre/post study (Lash et al., 2011). One pre/post study investigated a home-based exercise program (DeNysschen et al., 2014), and two studies investigated walking programs, including one RCT involving Nordic Walking (Fields, 2015), and one pre/post study investigating a self-directed walking program (Nyrop et al., 2014). One pre/post study investigated Tai Chi (Galantino et al., 2013), and two other pre/post studies investigated yoga (Jacobsen et al., 2015; Galantino et al., 2012).
Treatment with Ruta graveolens 5CH and Rhus toxicodendron 9CH may reduce joint pain and stiffness linked to aromatase inhibitors in women with early breast cancer: results of a pilot observational study
2016, HomeopathyCitation Excerpt :Furthermore, the long-term use of NSAIDs is associated with a number of side-effects, particularly gastrointestinal and cardiovascular morbidity.15–17 Other therapies such as increased physical activity or yoga18–20 and a treatment algorithm for AI-induced arthralgia have been investigated,21 but despite this, arthralgia remains the most common reason for the premature discontinuation of AI therapy, compromising the outcome of treatment.21,22 New medicines or treatment approaches are therefore required to limit the appearance or decrease the intensity of AI-associated musculoskeletal pain.