Effect of aerobic exercise on worst joint pain in postmenopausal breast cancer women receiving aromatase inhibitors: A systematic review and meta-analysis

Abstract

Aromatase inhibitor-induced musculoskeletal symptoms (AIMSS), especially joint pain, have been widely reported in postmenopausal women undergoing endocrine therapy for hormone receptor-positive breast cancer and are a major cause of treatment termination. Aerobic exercise has emerged as a promising nonpharmacological intervention to counteract AIMSS in this population. This study aimed to perform a systematic review and meta-analysis to assess the effect of aerobic exercise on aromatase inhibitor-induced worst joint pain in postmenopausal breast cancer. A systematic literature search was performed using ClinicalTrials.gov, PubMed, and the Cochrane Library that yielded 1415 records. Studies comparing the effect of aerobic exercise with usual care on the worst joint pain through brief pain inventory (BPI) scoring in postmenopausal women with breast cancer receiving aromatase inhibitor therapy were included. For each group, the mean change from baseline and standard deviation (SD) of worst joint pain (BPI score) were calculated. Mean differences (MDs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Subgroup analyses were conducted to explore heterogeneity based on exercise intervention. Three randomized controlled trials (n = 297) were included. Pooled analysis showed no significant overall effect of exercise compared with control (standardized mean difference [SMD] = -0.16; 95% CI [-1.45, 1.14]; p = 0.65; I² = 74%). Subgroup analysis indicated a significant difference by exercise type (p = 0.003), suggesting exercise modality influenced outcomes. Aerobic exercise, evaluated in two RCTs, significantly reduced worst joint pain (SMD = -0.41; 95% CI [-0.50, -0.32]; p = 0.01; I² = 0%), indicating consistent benefit across studies. In contrast, the single study assessing Nordic walking showed no significant improvement (SMD = 0.56; 95% CI [-0.08, 1.19]; p = 0.08). Risk-of-bias assessment revealed variability across studies, with one trial rated low risk, one with some concerns, and one at high risk, which may partly explain the observed heterogeneity (I² = 74%). Aerobic exercise interventions did not show an overall significant effect on the worst joint pain. However, subgroup analysis revealed that multi-component aerobic exercise programs were associated with significant pain reduction, while the study with only Nordic walking intervention was not. Considering the clinical burden of aromatase inhibitor-induced musculoskeletal symptoms, aerobic exercise can be a potentially useful non-pharmacologic adjunct to endocrine therapy. However, given the variation in the assessed risk of bias among the included studies, these outcomes should be interpreted with due caution. To confirm these results and determine the optimal exercise type and duration for managing aromatase inhibitor–associated musculoskeletal symptoms in breast cancer survivors, further large-scale trials are necessary.

Keywords

aerobic exercise / joint pain / breast cancer / post menopausal women / aromatase inhibitors

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