Effectiveness of acupuncture in managing aromatase inhibitor-related arthralgia in breast cancer: a systematic review and meta-analysis

Abstract

Objective: Breast cancer is the second most prevalent cause of mortality in women and the predominant malignancy type. However, breast cancer treatment faces challenges in managing aromatase inhibitor-induced arthralgia. Aromatase inhibitors have been shown to decrease recurrence risk in hormone receptor-positive cases; however, joint discomfort remains the primary adverse effect. Randomized clinical trials have evaluated the therapeutic outcomes of acupuncture for medication-related musculoskeletal complications. This comprehensive analysis sought to elucidate both the therapeutic efficacy and placebo responses associated with acupuncture intervention.

Methods: Two reviewers searched for randomized controlled trials (RCTs) in four English (PubMed, Embase, Web of Science, and the Cochrane Library) and four Chinese databases (CNKI, Wanfang Database, VIP, and SinoMed) from their inception to May 31, 2024. Methodological quality was assessed using the Cochrane risk of bias tool. Data were synthesized using random effects models and presented with forest plots.

Results: Seven trials involving 604 patients were included. The primary outcome and Brief Pain Inventory (BPI) score differed between the acupuncture and control groups (sham acupuncture or usual medication) in three subscales over the course of 6 weeks: worst pain: standardized mean difference (SMD) = −1.18, 95% confidence interval (CI): −1.74, −0.63, P < 0.001; pain-related interference: SMD = −0.87, 95% CI: −1.70, −0.05, P = 0.038; pain severity: SMD = −0.63, 95% CI: −1.22, −0.04, P = 0.036. No severe adverse events were reported in any study.

Conclusions: This meta-analysis showed that acupuncture is a safe and effective treatment for patients with breast cancer with aromatase inhibitor-induced arthralgia during the course of 6 weeks. Improvements in the blinding method and clarification of the total treatment recommendations and intervals need to be explored further.

Keywords

Acupuncture / Aromatase inhibitor-induced arthralgia / Breast cancer / Meta-analysis

Conflict of interest statement

Yi Guo is the editorial board member of this journal and other authors declare no conflict of interest.

Funding

This work was supported by the National Key R&D Program of China (2019YFC1712200-2019YFC1712204), the National Natural Science Foundation of China (82004467, 82030125), and the Youth Project of Traditional Chinese Medicine-Integration of Traditional and Western Medicine Projects of Tianjin Health Commission (No. 2025027).

Author contributions

All authors listed have made substantial, direct, and intellectual contributions to the work. Bo Chen and Yi Guo designed the study. Zheng Zhu, Yaman Zheng, and Xinru Yuan reviewed the literature and drafted the main manuscript. Baomin Dou, Liang Liu, Pei Yong Loh, and Aoxiang Chen had helped with literature search, data extraction. Bo Chen, Zheng Zhu, Peihong Ma, and Zelin Chen conducted the data analysis. All authors edited and reviewed and the manuscript.

Ethical approval of studies and informed consent

Not applicable.

Acknowledgments

None.

Data availability

All datasets generated in this study are included in the manuscript and supplementary files.

References

[1] Ghoncheh M, Pournamdar Z, Salehiniya H. Incidence and mortality and epidemiology of breast cancer in the world. Asian Pac J Cancer Prev 2016; 17(S3):43-46.

[2] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024;74(3):229-263.

[3] Mutebi M, Anderson BO, Duggan C, et al. Breast cancer treatment: a phased approach to implementation. Cancer 2020; 126(Suppl 10):2365-2378.

[4] Jayasekera J, Zhao A, Schechter C, et al. Reassessing the benefits and harms of risk-reducing medication considering the persistent risk of breast cancer mortality in estrogen receptor-positive breast cancer. J Clin Oncol 2023; 41(4):859-870.

[5] Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline update on ovarian suppression. J Clin Oncol 2016; 34(14):1689-1701.

[6] Burstein HJ, Somerfield MR, Barton DL, et al. Endocrine treatment and targeted therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: ASCO guideline update. J Clin Oncol 2021; 39(35):3959-3977.

[7] Lintermans A, Laenen A, Van Calster B, et al. Prospective study to assess fluid accumulation and tenosynovial changes in the aromatase inhibitor-induced musculoskeletal syndrome: 2-year follow-up data. Ann Oncol 2013; 24(2):350-355.

[8] Beckwée D, Leysen L, Meuwis K, et al. Prevalence of aromatase inhibitor-induced arthralgia in breast cancer: a systematic review and meta-analysis. Support Care Cancer 2017; 25(5):1673-1686.

[9] Gibson LJ, Dawson C, Lawrence DH, et al. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database Syst Rev 2007(1):CD003370.

[10] Murphy CC, Bartholomew LK, Carpentier MY, et al. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat 2012; 134(2):459-478.

[11] Greenlee H, DuPont-Reyes MJ, Balneaves LG, et al. Clinical practice guidelines on the evidence-based use of integrative therapies during and after breast cancer treatment. CA Cancer J Clin 2017;67(3):194-232.

[12] Kothawala P, Badamgarav E, Ryu S, et al. Systematic review and meta-analysis of real-world adherence to drug therapy for osteoporosis. Mayo Clin Proc 2007; 82(12):1493-1501.

[13] Lyman GH, Greenlee H, Bohlke K, et al. Integrative therapies during and after breast cancer treatment: ASCO endorsement of the SIO clinical practice guideline. J Clin Oncol 2018; 36(25):2647-2655.

[14] Liu BY, Chen B, Guo Y, et al. Acupuncture—a national heritage of China to the world: international clinical research advances from the past decade. Acupunct Herb Med 2021; 1(2):65-73.

[15] Han JS. Acupuncture: neuropeptide release produced by electrical stimulation of different frequencies. Trends Neurosci 2003; 26(1):17-22.

[16] Pomeranz B. Scientific research into acupuncture for the relief of pain. J Altern Complement Med 1996; 2(1):53-60; discussion 73.

[17] Li A, Lao L, Wang Y, et al. Electroacupuncture activates corticotrophin-releasing hormone-containing neurons in the paraventricular nucleus of the hypothalammus to alleviate edema in a rat model of inflammation. BMC Complement Altern Med 2008; 8:20.

[18] Dhond RP, Kettner N, Napadow V. Neuroimaging acupuncture effects in the human brain. J Altern Complement Med 2007; 13(6):603-616.

[19] Langevin HM, Yandow JA. Relationship of acupuncture points and meridians to connective tissue planes. Anat Rec 2002; 269(6):257-265.

[20] Kronenberg F, Fugh-Berman A. Complementary and alternative medicine for menopausal symptoms: a review of randomized, controlled trials. Ann Intern Med 2002; 137(10):805-813.

[21] Berman BM, Langevin HM, Witt CM, et al. Acupuncture for chronic low back pain. N Engl J Med 2010; 363(5):454-461.

[22] Liu LL. Clinical observation of warm acupuncture in the treatment of aromatase inhibitor-related osteoarticular symptoms. Guangzhou Univ Tradit Chin Med 2020.

[23] Li J, Huang M, Lin MD, et al. Clinical effect of Canggui Tanxue acupuncture at ashi point in the treatment of muscle, bone and joint pain induced by aromatase inhibitor of breast cancer. China Med Herald 2019; 16:132-135.

[24] Hershman DL, Unger JM, Greenlee H, et al. Effect of acupuncture vs sham acupuncture or waitlist control on joint pain related to aromatase inhibitors among women with early-stage breast cancer: a randomized clinical trial. JAMA 2018; 320(2):167-176.

[25] Ye J, Wang B, Lv XA, et al. Clinical study of acupuncture intervention in muscle, bone and joint pain caused by aromatase inhibitors in the treatment of breast cancer. Shanghai J Acup Moxib 2015; 34:642-646.

[26] Mao JJ, Xie SX, Farrar JT, et al. A randomised trial of electro-acupuncture for arthralgia related to aromatase inhibitor use. Eur J Cancer 2014; 50(2):267-276.

[27] Bao T, Cai L, Giles JT, et al. A dual-center randomized controlled double blind trial assessing the effect of acupuncture in reducing musculoskeletal symptoms in breast cancer patients taking aromatase inhibitors. Breast Cancer Res Treat 2013; 138(1):167-174.

[28] Crew KD, Capodice JL, Greenlee H, et al. Randomized, blinded, sham-controlled trial of acupuncture for the management of aromatase inhibitor-associated joint symptoms in women with early-stage breast cancer. J Clin Oncol 2010; 28(7):1154-1160.

[29] Chen L, Lin CC, Huang TW, et al. Effect of acupuncture on aromatase inhibitor-induced arthralgia in patients with breast cancer: a meta-analysis of randomized controlled trials. Breast 2017; 33:132-138.

[30] Page MJ, McKenzie JE, Bossuyt PM, et al. Updating guidance for reporting systematic reviews: development of the PRISMA 2020 statement. J Clin Epidemiol 2021; 134:103-112.

[31] Wang XQ, Chen YL, Liu YL, et al. Reporting items for systematic reviews and meta-analyses of acupuncture: the PRISMA for acupuncture checklist. BMC Complement Altern Med 2019; 19(1):208.

[32] Farrar JT, Young JP Jr, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001;94(2):149-158.

[33] Bauml J, Xie SX, Farrar JT, et al. Expectancy in real and sham electroacupuncture: does believing make it so? J Natl Cancer Inst Monogr 2014; 2014(50):302-307.

[34] Fei YT, Cao HJ, Xia RY, et al. Methodological challenges in design and conduct of randomised controlled trials in acupuncture. BMJ 2022; 376:e064345.

[35] Zhang Z, Li RR, Chen Y, et al. Integration of traditional, complementary, and alternative medicine with modern biomedicine: the scientization, evidence, and challenges for integration of traditional Chinese medicine. Acupunct Herb Med 2024; 4(1):68-78.

[36] Zeng YZ, Chen SY. Outcome measure selection and sample size estimation for clinical research. Med J Peking Union Med Coll Hosp 2018; 9(1):87-92.

[37] Huang SR. After the effect of acupuncture analgesia and acupuncture, acupuncture tolerance frequency. Chin J Pain Med 2006; 12(6):360-362.

[38] Tang DA. Introduction to Experimental Acupuncture. Tianjin: Tianjin Science and Technology Press; 1986:221-225.

[39] Robinson CL, Berger A, Sottosanti E, et al. Acupuncture as part of multimodal analgesia for chronic pain. Orthop Rev (Pavia) 2022; 14(3):38321.

[40] Coutaux A. Non-pharmacological treatments for pain relief: TENS and acupuncture. Joint Bone Spine 2017; 84(6):657-661.

[41] Yang FW, Ji ZC, Zhang MY, et al. Causes and countermeasures of waste in clinical research of Chinese medicine. Chin J Evid Based Med 2018; 18(11):1212-1215.