Acupuncture for Aromatase Inhibitor-Induced Arthralgia in Breast Cancer: An Umbrella Review.

Background: Acupuncture therapy shows promise in managing aromatase inhibitor-induced arthralgia (AIA) among breast cancer patients. An umbrella review synthesizes findings from systematic reviews and meta-analyses (SRs/MAs) to assess its effectiveness. Summary: This umbrella review aimed to evaluate the effectiveness of acupuncture therapy in treating AIA among breast cancer patients by analyzing existing evidence from SRs/MAs. Key Messages: Six SRs/MAs were analyzed, revealing shortcomings in reporting quality, methodological quality, and evidence quality assessment. Comprehensive searches across eight electronic databases were conducted. PRISMA, AMSTAR 2, and GRADE were utilized to assess reporting, methodological quality, and evidence quality, respectively. Despite methodological shortcomings, a recent meta-subgroup analysis suggests the efficacy of acupuncture therapy for AIA patients, recommending a 10-session treatment course. Conclusion: Acupuncture is identified as a secure and effective remedy for AIA sufferers, yet further high-quality research is needed to strengthen the evidence base and endorse acupuncture as a viable treatment option.

Aromatase inhibitor-induced arthralgia ameliorated by Mediterranean diet and active lifestyle guided by continuous glucose monitoring: a case report and review of the literature.

Aromatase inhibitors (AIs) are a cornerstone adjuvant treatment of many hormone receptor-positive breast cancers, and nearly half of women taking aromatase inhibitors suffer from AI-induced arthralgia (AIA), also known as AI-associated musculoskeletal syndrome (AIMSS), for which there are limited evidence-based treatments. Pharmacologic management and complementary methods including supplements, exercise, physical therapy, yoga, acupuncture, and massage have all shown mixed results. Comprehensive diet and lifestyle strategies are understudied in AIA/AIMSS despite their disease-modifying effects across many chronic conditions. Here we report a case of a woman with stage 2 estrogen and progesterone receptor-positive invasive ductal carcinoma on adjuvant anastrozole whose AI-induced arthralgia was durably controlled through a Mediterranean plant-forward diet and daily physical activity guided by continuous glucose monitoring. We posit that diet and a lifestyle inclusive of daily physical activity constitute a low-cost, low-risk, and potentially high-reward strategy for controlling common AI-induced musculoskeletal symptoms and that more investigation in this arena, including well-designed randomized trials, is warranted.

Aromatase-Inhibitor-Induced Musculoskeletal Inflammation Is Observed Independent of Oophorectomy in a Novel Mouse Model.

Aromatase Inhibitors (AIs) block estrogen production and improve survival in patients with hormone-receptor-positive breast cancer. However, half of patients develop aromatase-inhibitor-induced arthralgia (AIIA), which is characterized by inflammation of the joints and the surrounding musculoskeletal tissue. To create a platform for future interventional strategies, our objective was to characterize a novel animal model of AIIA. Female BALB/C-Tg(NFκB-RE-luc)-Xen mice, which have a firefly luciferase NFκB reporter gene, were oophorectomized and treated with an AI (letrozole). Bioluminescent imaging showed significantly enhanced NFκB activation with AI treatment in the hind limbs. Moreover, an analysis of the knee joints and legs via MRI showed enhanced signal detection in the joint space and the surrounding tissue. Surprisingly, the responses observed with AI treatment were independent of oophorectomy, indicating that inflammation is not mediated by physiological estrogen levels. Histopathological and pro-inflammatory cytokine analyses further demonstrated the same trend, as tenosynovitis and musculoskeletal infiltrates were detected in all mice receiving AI, and serum cytokines were significantly upregulated. Human PBMCs treated with letrozole/estrogen combinations did not demonstrate an AI-specific gene expression pattern, suggesting AIIA-mediated pathogenesis through other cell types. Collectively, these data identify an AI-induced stimulation of disease pathology and suggest that AIIA pathogenesis may not be mediated by estrogen deficiency, as previously hypothesized.

Feasibility Trial to Evaluate Tendon Stiffness Obtained from Shear Wave Elastography Imaging as a Biomarker of Aromatase Inhibitor-Induced Arthralgias.

Aromatase inhibitor-induced arthralgia (AIA) comprises significant, activity-limiting musculoskeletal symptoms, including joint pain, myalgia, and joint stiffness. We conducted a prospective feasibility study in postmenopausal women diagnosed with early-stage (0-3) hormone receptor positive (HR+) breast cancer who were candidates for treatment with adjuvant AI therapy (n = 16). Tendons of the hands and wrists and the median nerve were imaged using gray-scale and power Doppler ultrasound (US) and US SWE. Arthralgia symptoms were evaluated using the Breast Cancer Prevention Trial (BCPT) Symptom Checklist musculoskeletal subscale (MS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and stiffness subscales. At baseline, there were significant differences in the SW velocities of tendons between dominant and nondominant hands. Increased velocity in 2 of 6 tendons and the median nerve was associated with greater pain at baseline, whereas slower velocity of the extensor digitorum tendon (suggesting decreased stiffness) was associated with a higher WOMAC stiffness score. Increased SW velocity (suggestive of increased stiffness) at baseline in the abductor pollicis longus tendon was associated with a worsening of all three pain and stiffness measures by 6 months. Future studies should evaluate SWE scores related to AIA outcomes in a larger sample size.

Aromatase Inhibitor-Associated Musculoskeletal Syndrome: Understanding Mechanisms and Management.

Aromatase inhibitors (AIs) are a key component in the chemoprevention and treatment of hormone receptor-positive (HR+) breast cancer. While the addition of AI therapy has improved cancer-related outcomes in the management of HR+ breast cancer, AIs are associated with musculoskeletal adverse effects known as the aromatase inhibitor-associated musculoskeletal syndrome (AIMSS) that limit its tolerability and use. AIMSS is mainly comprised of AI-associated bone loss and arthralgias that affect up to half of women on AI therapy and detrimentally impact patient quality of life and treatment adherence. The pathophysiology of AIMSS is not fully understood though has been proposed to be related to estrogen deprivation within the musculoskeletal and nervous systems. This review aims to characterize the prevalence, risk factors, and clinical features of AIMSS, and explore the syndrome's underlying mechanisms and management strategies.

Acupuncture for Arthralgia Induced by Aromatase Inhibitors in Patients with Breast Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Aromatase inhibitor-induced arthralgia (AIA) is the most common side effect of aromatase inhibitors (AIs) used in breast cancer patients and is related to the rate of adherence to AIs. The clinical effects of acupuncture on AIA have been assessed by some randomized controlled trials (RCTs). However, some studies reported that acupuncture was effective, while others claimed that it was ineffective. To clarify the clinical and placebo effects of acupuncture in treating AIA, we conducted this meta-analysis. METHODS: Two reviewers (XL and GW) independently searched for RCTs in 5 English databases (PubMed, Web of Science, Embase, Springer, Cochrane Library) and 4 Chinese databases (China National Knowledge Infrastructure Database (CNKI), SinoMed, VIP and Wanfang Database) from their inception to 30 November 2019. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this meta-analysis was performed by fixed or random-effects models, and data were pooled with mean differences (MDs). RESULTS: Seven trials involving 603 patients were reviewed. The primary outcome, the Brief Pain Inventory (BPI) score, significantly differed between the acupuncture and control groups [pain-related interference: MD = -1.89, 95% confidence interval (CI) [-2.99, -0.79], Z = 3.36 (P = .008 < .05), pain severity: MD = -1.57, 95% CI [-2.46, -0.68], Z = 3.45 (P = .0006 < .05), worst pain: MD = -2.31, 95% CI [-3.15, -1.48], Z = 5.47 (P < .0001 < .05)]. No severe adverse events were reported in any study. CONCLUSION: This meta-analysis showed that acupuncture is a safe and effective treatment for breast cancer patients with AIA. Additional research with improved blinding methods is warranted to further explore the nature of non-specific and placebo effects in true and sham acupuncture.

The Effect of Exercise on the Alleviation of Side Effects Induced by Aromatase Inhibitors in Postmenopausal Breast Cancer Patients.

PURPOSE OF REVIEW: Aromatase inhibitors (AIs) are effective in treating postmenopausal women suffering from estrogen receptor-positive breast cancer (BC). However, AIs are also commonly associated with a number of side effects which decrease the quality of life (QoL) of the patients. This review focuses on the effects of exercise interventions on reducing the side effects commonly experienced by BC patients on AI treatment. RECENT FINDINGS: Recent studies in the literature support that exercise interventions are feasible and improve body composition, aromatase inhibitor-induced Arthralgia (AIIA), and the overall QoL of BC patients. Successful implementation of longitudinal exercise interventions is expected to improve the QoL of BC patients on AI treatment. Future studies should therefore be carried out with a larger number of postmenopausal BC patients on AI treatment to (a) investigate the effects of exercise interventions on depression, cognitive decline, and cardiotoxicity and (b) address the motivation that should be used to keep BC survivors engaged in exercise intervention programs.

Randomized controlled trial of high-dose versus standard-dose vitamin D3 for prevention of aromatase inhibitor-induced arthralgia.

PURPOSE: Half of hormone receptor-positive (HR+) breast cancer patients will develop joint pain, termed aromatase inhibitor-induced arthralgia (AIA), while taking aromatase inhibitor therapy. Though there is no universally accepted effective treatment for AIA, there has been some evidence to support high-dose vitamin D as a treatment. METHODS: We randomized post-menopausal women who were beginning adjuvant AI therapy to receive standard-dose vitamin D3 (800 IU daily for 52 weeks), or high-dose vitamin D3 (50,000 IU weekly for 12 weeks, followed by 2000 IU daily for 40 weeks). The primary end point was development of AIA. The trial was designed to enroll 184 patients. This futility analysis was performed after 93 patients were enrolled. RESULTS: The high-dose vitamin D regimen was effective in raising serum vitamin D levels, but there was no significant difference in development of AIA between the two arms. In the high-dose arm, 25 patients (54%) developed AIA, compared to 27 patients (57%) in the standard-dose arm. The planned futility analysis was positive; thus, the study was terminated. Neither baseline vitamin D nor 12-week vitamin D level was predictive of AIA development. CONCLUSION: Although vitamin D levels were increased in the high-dose arm, there was no significant signal for benefit of high-dose vitamin D supplementation for AIA prevention in this unblinded trial. This study, along with several others, implies that vitamin D likely does not play a significant role in AIA for the majority of patients.

Auricular Point Acupressure to Manage Aromatase Inhibitor-Induced Arthralgia in Postmenopausal Breast Cancer Survivors: A Pilot Study.

PURPOSE/OBJECTIVES: To assess the feasibility of auricular point acupressure to manage aromatase inhibitor-induced arthralgia.
. DESIGN: Wait list control design.
. SETTING: Outpatient clinics and oncology center.
. SAMPLE: 20 women with aromatase inhibitor-induced arthralgia.
. METHODS: After baseline data were collected, participants waited one month before they received acupressure once per week for four weeks at a convenient time. The baseline data served as the control comparison. Self-reported measures and blood samples were obtained at baseline, at preintervention, weekly during the intervention, and at post-intervention.
. MAIN RESEARCH VARIABLES: The primary outcomes included pain intensity, pain interference, stiffness, and physical function. Inflammatory cytokines and chemokines were tested.
. FINDINGS: After the four-week intervention, participants reported decreases in worst pain and pain interference, and improvements in physical function, cancer-related symptom severity, and interference. The proinflammatory cytokines and chemokines displayed a trend of a mean percentage reduction. The anti-inflammatory cytokine interleukin-13 increased from pre- to postintervention.
. CONCLUSIONS: Auricular point acupressure is feasible and may be effective in managing arthralgia in breast cancer survivors.
. IMPLICATIONS FOR NURSING: Nurses can administer acupressure in clinical settings, which could enhance the management of aromatase inhibitor-induced arthralgia and contribute to a shift from traditional disease-based biomedical models to a broader, integrative, medical paradigm for managing aromatase inhibitor-induced arthralgia.

Effect of acupuncture on aromatase inhibitor-induced arthralgia in patients with breast cancer: A meta-analysis of randomized controlled trials.

PURPOSE: Aromatase inhibitor (AI)-induced arthralgia (AIA) is a common side effect that may lead to premature discontinuation of effective hormonal therapy in patients with breast cancer. Acupuncture may relieve joint pain in patients with AIA. We conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the effectiveness of acupuncture in pain relief in AIA. METHODS: The PubMed, Embase, Cochrane Library, and Scopus databases and the ClinicalTrials.gov registry were searched for studies published before February 2017. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate the pooled effect size by using a random effect model. Pain was assessed using the Brief Pain Inventory (BPI) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3-4, 6-8, and 12 weeks. Secondary outcomes included disability level, upper extremity function, physical performance, and quality of life. RESULTS: Five trials involving 181 patients were reviewed. Significant pain reduction was observed after 6-8 weeks of acupuncture treatment. Patients receiving acupuncture showed a significant decrease in the BPI worst pain score (weighted mean difference [WMD]: -3.81, 95% confidence interval [CI]: -5.15 to -2.47) and the WOMAC pain score (WMD: -130.77, 95% CI: -230.31 to -31.22) after 6-8 weeks of treatment. One of the 4 trials reported 18 minor adverse events in 8 patients during 398 intervention episodes. CONCLUSION: Acupuncture is a safe and viable nonpharmacologic treatment that may relieve joint pain in patients with AIA. Additional studies involving a higher number of RCTs are warranted.