Effects of Acupuncture and Moxibustion on Breast Cancer-Related Lymphedema: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Objective:

The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to evaluate the effects of acupuncture and moxibustion (AM) in women with breast cancer-related lymphedema (BCRL).

Methods:

We retrieved RCTs published before January 24, 2021, from the MEDLINE, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Chongqing VIP (VIP), and Wanfang databases. RCTs that compared acupuncture and/or moxibustion intervention with other treatments were included. A random effects or fixed effects model was used based on the heterogeneity findings. Study quality was evaluated using the Cochrane risk of bias tool.

Results:

We included 14 RCTs in the analyses, of which 4 RCTs adopted acupuncture, 4 RCTs used moxibustion, and the rest used both. AM significantly reduced arm circumference at the elbow crease compared to routine care (Mean deviation (MD) = −7.26, 95% confidence interval (CI) = −8.30 to −6.21, P < .00001). There was a significant difference between AM and diosmin tablets in the effective index for upper limb lymphedema (MD = 24.68, 95% CI = 24.82-30.53, P < .00001), the range of motion of the shoulder during protraction (MD = 6.77, 95% CI = 2.81-10.73, P = .0008), and adduction (MD = 4.17, 95% CI = 1.02-7.32, P = .01). There was a significant difference between moxibustion and pneumatic circulation (MD = −0.51, 95% CI = −0.85 to −0.17, P = .003) in the visual analog score (VAS) for swelling. Finally, compared to the blank control, acupuncture reduced the VAS for pain (MD = −1.33, 95% CI = −1.52 to −1.15, P < .00001; heterogeneity (I²) = 0%, P = .57).

Conclusion:

Our results suggest that AM is effective in the treatment of BCRL. AM may reduce arm circumference at the elbow crease (compared to routine care), increase effective index for upper limb lymphedema (compared to oral diosmin tablets), improve the range of motion of the shoulder during protraction and adduction (compared to oral diosmin tablets), and decrease the VAS for both swelling (compared to pneumatic circulation) and pain (compared to blank control).

Keywords

acupuncture moxibustion breast cancer-related lymphedema

Introduction

Breast cancer (BC) is the most frequently diagnosed cancer among women worldwide, and its incidence is gradually increasing.¹ Fortunately, with the advancement of early screening and diagnosis, the 5-year survival rate of BC patients is almost 90%.² However, these survivors are at an increased risk of long-term complications because of surgery as well as radiation-related therapeutic exposures.³ BC-related lymphedema (BCRL) is one of the most frequent complications of BC and its treatment procedures, which has a profound effect on the patients’ quality of life and upper limb function.⁴ Further, swelling can cause physical discomfort such as fatigue, stiffness, pain, heaviness, tension, numbness, and restricted mobility, which can trigger mental disorders and anxiety in women with lymphedema.^5,6

Lymphedema cannot be completely cured, although there are some methods for its prevention and management.⁷ Consequently, limiting the development of edema and improving symptoms have become a common challenge faced by clinicians and patients. Current treatments for BCRL include education during the decompression phase, the use of fitted compression garments during maintenance, manual lymphatic drainage, compression bandaging, and exercise; but the efficacy of these measures remains uncertain.⁷

Acupuncture and moxibustion (AM) have long been used in the treatment of various diseases and physiological disorders in Chinese medicine, and it is becoming increasingly popular worldwide. Acupuncture involves the insertion of fine metal needles into specific areas of the body (acupuncture points or acupoints) to facilitate the recovery of health. In contrast to the mechanical stimulation of acupuncture, the effect of moxibustion is mainly realized by thermal stimulation when the moxa stick is ignited. Clinically, acupuncture and moxibustion can be used alone or in combination. In recent years, studies have been conducted on the treatment of BCRL with AM, and preliminary results have shown the therapeutic potential of AM. Some studies have demonstrated that AM may stabilize symptoms and reduce arm circumference in cases with BCRL.^8-10 Some studies suggest that AM is well tolerated, but there is no significant advantage in changing the arm circumference of BCRL patients.^11,12 These differences may be due to different study designs, statistical analyses, and sample sizes. Therefore, it is crucial to determine whether AM is safe, feasible, and effective in patients with BCRL. Here, we performed a systematic review and meta-analysis of clinical randomized controlled trials (RCTs) to answer this question.

Methods

This protocol followed the PRISMA guidelines (http://www.prisma-statement.org/). Our study was registered on the PROSPERO website with identifier CRD42021241686.

Literature Search

We searched the relevant English/Chinese medical literature in the MEDLINE (via PubMed), EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Chongqing VIP Chinese Science and Technology Periodical (VIP), and Wanfang databases, published until January 24, 2021. The search terms used were as follows: breast neoplasms, breast cancer, breast carcinoma, lymphedema, acupuncture, needle, needling, moxibustion, moxa, moxabustion, moxacone, randomized controlled trial, controlled clinical trial, randomly, and RCT. Chinese translations of these search terms were used for the Chinese databases. The database search strategy is provided in Supplemental Appendix 1. Unrelated articles were automatically excluded based on their titles and abstracts. We read the rest of the articles carefully to see if they met the selection criteria. All searches were independently conducted by 2 researchers, and a third researcher arbitrated the disputes.

Study Selection Criteria

Types of studies

RCTs were included.

Types of participants

The patients were women with lymphedema, which was caused by BC and its treatment procedures (surgery and/or radiotherapy). There were no restrictions on participants’ BC stage, lymphedema grade, age, or country.

Types of interventions

In the treatment group, only needle acupuncture was allowed, and other forms of acupuncture (such as point injection, laser acupuncture, or electroacupuncture) were not allowed. Similarly, for moxibustion treatment, only burning Artemisia vulgaris was allowed and other herbs were not included. The treatment group received acupuncture and/or moxibustion without any restriction of manipulation techniques. The control group received any other treatment except acupuncture or moxibustion.

Types of outcomes

Any result involving changes in edema was considered a primary outcome, which was assessed by measuring the circumference of the arm or the volume of the fluid content in the limb. The secondary outcomes included visual analog score (VAS) for swelling/pain, range of motion (ROM), quality of life scores, bioimpedance, and the rate of AM-related adverse events (AEs) (such as bruises, hematomas, pain, allergies, burns, local infections, cough, or nausea).

Articles that met any of the following conditions were excluded: (1) unavailable original full text, (2) duplicating published literature, (3) incomplete or missing research data, (4) studies without comparable baselines, and (5) animal experiments, letters, reviews, or commentaries.

Quality Assessment and Data Extraction

Cochrane Risk of Bias Assessment tool (Cochrane Collaboration) was used to assess the risk of bias.¹³ The following types of bias were assessed: (1) random sequence generation, (2) allocation concealment, (3) blinding of participants and personnel, (4) blinding of outcome assessment, (5) incomplete outcome data, (6) selective reporting, and (7) other bias. Each item was classified into 3 types: low-risk, high-risk, and unclear risk. The quality of the included trials was independently evaluated by 2 reviewers, and disagreements were resolved by a third researcher.

Equivalent information collected from the selected studies: first author’s name, year of study, age of the participants, sample size, inclusion criteria, status of lymphedema, intervention, primary acupoints, course of treatment, retention time, and outcomes. Two researchers checked the extracted data for consistency, and a third researcher arbitrated any dispute.

Statistical Analysis

Dichotomous data were analyzed using odds ratio with 95% CIs. For continuous outcomes, data were analyzed using the mean difference with 95% CIs. A meta-analysis of the trials was carried out when at least 2 trials that analyzed the data for a specific outcome were included.

Heterogeneity among the studies was detected using P and I² statistics.¹⁴ A random effects model was adopted when heterogeneity was observed (P < .05 and/or I² > 50%); otherwise, a fixed effects model was adopted. Subgroup and sensitivity analyses were performed to dissect the heterogeneity. Clinical heterogeneity was defined as differences in participants, treatment, outcome characteristics, or research setting. When more than 10 studies were included, publication bias was investigated using the funnel plot, Begg’s test, and Egger’s test. A significant difference was assumed at P < .05.^15,16

All data were analyzed using the STATA 12.0 (StataCorp LP, College Station, TX, USA) and RevMan 5.3 (Cochrane Collaboration, Oxford, UK) software.

Results

Study Selection

The PRISMA flow diagram (Figure 1) displays the selection process.¹⁷ We found 822 articles by searching the databases (MEDLINE, EMBASE, Cochrane Library, Web of Science, CNKI, VIP, and Wanfang). After excluding 69 duplicate articles, 2 researchers conducted independent review and exclusion. Based on the title and abstract, 713 articles did not meet the selection criteria and were excluded. Of the remaining 40 papers, 24 were excluded for the following reasons: 3 studies were duplicated, 3 studies were not RCTs, the population did not include BCRL patients in 7 studies, in 10 studies the experimental intervention was not acupuncture and/or moxibustion, and 3 articles did not report relevant outcomes. Finally, 14^12,18-30 articles were included in our analysis.

Figure 1.

Flow diagram of studies selection.

Study Characteristics

Fourteen RCTs with 758 participants were included in this review. Four^12,20,21,29 of the included RCTs were published in English, and the remaining^{18,19,22-28,30} were published in Chinese. One RCT¹² was conducted in the USA, 1 RCT²⁰ was conducted in Australia, and the remaining^18,19,21-30 were conducted in China. The results of 13 RCTs^{12,18,19,21-30} involved changes in arm circumference, but the measurement methods were not uniform. The secondary outcomes in the included RCTs were bioimpedance, shoulder joint ROM, VAS for pain, VAS for swelling, quality of life scores, and AEs. Four studies^12,20,28,29 described the follow-up. The summarized characteristics of the 14 RCTs are presented in Table 1.

Table 1.

Characteristics of Included Randomized Controlled Trials.

Authors	Country	Age (years)	Sample Size E/C	The affected limb status at baseline	Drop out	AEs	Follow-up	Outcomes
Zhao et al¹⁸	China	32-76 mean: 46.8	46/46	The circumference of the affected side at the elbow was larger than that of the contralateral arm.	—	UK	UK	The circumference at elbow crease.
Huang et al¹⁹	China	30-73 mean: 45.5	31/31	The affected limb was swollen.	—	UK	UK	The circumference at elbow crease.
Smith et al²⁰	Australia	E 63.4 ± 7.4 C 57.0 ± 8.4	10/10	Exceeding the previously determined threshold for lymphoedema with bioimpedance for at least one 10 cm segment.	E: N = 1 Withdrew consent (N = 1) C: N = 2 Withdrew consent (N = 2)	Uncomfortable (N = 1)	3 mo	Bioimpedance.
Yao et al²¹	China	E 56.2 ± 5.82 C 55.8 ± 5.02	15/15	Circumference of the affected arm >3 cm greater than that of the contralateral arm. Patients had upper-limb lymphedema symptoms including stiff or hard skin and impaired ROM in the shoulder joint.	—	No AEs occurred	UK	1. EIL (wrist crease, 10 cm proximal to wrist crease, elbow crease, 10 cm proximal to elbow crease, and overall). 2. Shoulder joint ROM. 3. QLQ- Likert.
Jiao²²	China	E 45.62 ± 3.52 C 45.57 ± 3.50	15/15	The circumference of the affected side at the elbow was larger than that of the contralateral arm.	—	UK	UK	The circumference at elbow crease.
Zhan and Lou²³	China	30-70 57.84 ± 4.48	30/30	The total circumference of the affected side (the sum of the measured values at the elbow stripe and 10 cm, 20 cm, 30 cm and 40 cm above the elbow stripe) was 3-6 cm larger than that of the contralateral arm.	—	UK	UK	1. The difference between the total circumference (the sum of the measured values at the elbow stripe and 10 cm, 20 cm, 30 cm and 40 cm above the elbow stripe) of the affected arm and that of the contralateral arm. 2. VAS for pain.
Bao et al¹²	USA	E 65 (54, 71) C 58 (49, 70)	40/42	The affected arm circumference >2 cm larger than the unaffected arm in at least one of 2 sites (10 cm above or 5 cm below the olecranon process). Lymphedema diagnosed as stage II used International Society of Lymphology.	E: N = 4 Lost follow up (N = 1) Due to AE (N = 1) Withdrew consent (N = 2) C: N = 5 Withdrew consent (N = 5)	Bruises (N = 45) Hematoma (N= 2) Pain (N= 2) Skin infection (N = 1)	3 months	1. The maximum difference between the circumference of the affected arm and that of the contralateral arm. 2.Bioimpedance.
Wu²⁴	China	E 56.55 ± 4.64 C 56.73 ± 4.37	30/30	The total circumference (the sum of the measured values at 20 cm, 15 cm, 10 cm and 5 cm above and below the elbow, as well as at the middle of the palm and the wrist) of the affected side larger than that of the contralateral arm.	—	UK	UK	1. The difference between the total circumference (add the values measured at 20, 15, 10, and 5 cm above and below the elbow, as well as at the middle of the palm and the wrist) of the affected arm and that of the contralateral arm. 2. VAS for pain.
Ba²⁵	China	E 47.4 ± 4.3 C 46.3 ± 3.2	30/28	There was damage to the lymphatic system but no obvious swelling; local tissue edema with or without depression; local edema was more obvious than before, with obvious depression. The main symptoms of the affected limb were edema, pain, stiffness and dysfunction.	—	Uncomfortable (N = 2) Scald (N = 1)	UK	The circumference at 10, 20, 30, and 40 cm above the ulnar styloid process.
Liu et al²⁶	China	E 46.37 ± 14.53 C 49.32 ± 13.22	40/40	With the elbow joint extended, the circumference of the affected limb at 10 cm on the elbow striae was more than 3 cm larger than the circumference of the same part of the contralateral arm.	—	UK	UK	1. EIL (10 cm proximal to elbow crease). 2. Shoulder joint ROM. 3. QOL-UK.
Liu²⁷	China	E 55 ± 11 C 55 ± 10	30/30	The circumference of the affected side at the transverse wrist, 10 cm above the wrist and 10 cm above the elbow were all larger than that of the contralateral arm.	—	UK	UK	1. The difference between the circumference of the affected arm and that of the contralateral arm (10 cm proximal to elbow crease). 2. VAS for swelling. 3.QOL-UK.
Shen²⁸	China	E 59.67 ± 5.38 C 56.88 ± 5.97	24/24	The affected arm circumference >2 cm larger than the unaffected arm in at least one of 4 sites (wrist crease, 10 cm proximal to wrist crease, elbow crease, or 10 cm proximal to elbow crease). There was a marked sensation of swelling in the affected limb.	E: N = 2 Due to AE (N = 2) C: N = 3 Withdrew consent (N = 3)	Severer swelling(N = 1) Coughing (N = 1) Scald (N = 1)	1 mo	1. The circumference at wrist crease, 10 cm proximal to wrist crease, elbow crease, and 10cm proximal to elbow crease. 2. VAS for swelling. 3. EORTC - QLQ.
Wang et al²⁹	China	E 59.42 ± 7.02 C 58.25 ± 6.19	24/24	Circumference of the affected arm ≥2 cm greater than that of the contralateral arm.	E: N = 1 Withdrew consent (N = 1) C: N = 2 Withdrew consent (N = 2)	No AEs occurred	1 mo	1. The circumference at wrist crease, 10cm proximal to wrist crease, elbow crease, and 10 cm proximal to elbow crease. 2. The affected limb circumference mean value. 3. VAS for swelling.
Zhang et al³⁰	China	E 57.25 ± 7.19 C 58.36 ± 8.12	14/14	The affected arm circumference >2 cm larger than the unaffected arm (the average of wrist crease, 10 cm proximal to wrist crease, elbow crease, and 10 cm proximal to elbow crease). There was a marked sensation of swelling or joint dysfunction in the affected limb.	E: N = 1 Due to AE (N = 1) C: N = 1 Withdrew consent (N = 1)	UK	UK	1. The affected limb circumference mean value. 2. VAS for swelling. 3. QLQ - CCC.

Abbreviations: AE: adverse event; UK: unknown; N: number of patients; EIL: effective index for upper-limb lymphedema, EIL (%) = (upper-limb arm circumference before treatment – upper-limb arm circumference after treatment)/(upper-limb circumference of the affected arm before treatment – upper-limb circumference of the unaffected arm before treatment); ROM: range of motion; QLQ – Likert: Likert scale was used to evaluate quality of life; VAS: visual analog score; QOL-UK: unknown quality of life scale; EORTC – QLQ: Core Quality of Life Scale developed by the European Organization for Research and Treatment of Cancer; QLQ – CCC: Chemobiotherapy Quality of Life Scale for Cancer Patients in China.

AM and Control Interventions

Of the 14 RCTs, 4 RCTs^12,20,23,24 adopted acupuncture, 4^19,28-30 used moxibustion, and the rest^{18,21,22,25-27} used both. The most commonly used acupoints were TE.5 (Waiguan), LI.15 (Jianyu), LI.11 (Quchi), LI.14 (Binao), SP.9 (Yinlingquan), TE.14 (Jianliao), and LI.4 (Hegu). The frequency of AM ranged from once a week to once per day. Retention time ranged from 5 to 30 min. The total number of AM treatments ranged from 7 to 45, while the course of AM treatment ranged from 2 to 9 weeks.

In most cases, the experimental group and the control group had a similar treatment frequency. One study¹² used a wait-list control comparison. Four RCTs^19,21,25,26 used oral drug therapy as control; 1 study¹⁹ used hydrochlorothiazide and spironolactone, while the rest^21,25,26 used diosmin tablets. In 3 studies,^23,24,27 the interventions used in the control group were also used as the basic treatment in the experimental group. Three RCTs^28-30 chose pneumatic circulation as a control, while the control group in 3 other studies^18,20,22 received routine care.

The interventions of each trial are presented in Table 2.

Table 2.

Specific Intervention Measures for the Experimental Group and the Control Group.

Authors	Experimental group	Primary Acupoints	Course of treatment	Retention time	Control group
Authors	Intervention	Primary Acupoints	Course of treatment	Retention time	Intervention
Zhao et al¹⁸	AM	LI.4 (Hegu), LI.15 (Jianyu), TE.5 (Waiguan), LI.11 (Quchi), GB.21 (Jianjin), SI.9 (Jianzhen), TE.14 (Jianliao), LI.14 (Binao), LU.1 (Zhongfu), LU.7 (Lieque), CV.9 (Shuifen), SP.9 (Yinlingquan), ST.36 (Zusanli), LR.3 (Taichong), and Ashi points.	5 × per week for 3 wk (Nt = 15)	20 min	Usual care for 3 wk (Nt-UK).
Huang et al¹⁹	Moxibustion + Functional exercises	LI.4 (Hegu), LI.15 (Jianyu), TE.5 (Waiguan), LI.11 (Quchi), GB.21 (Jianjin), SI.9 (Jianzhen), TE.14 (Jianliao), LI.14 (Binao), LU.7 (Lieque), CV.9 (Shuifen), SP.9 (Yinlingquan), and Ashi points.	5 × per week for 6 wk (Nt = 30)	20 min	Functional exercises for 6 wk (Nt-UK) + Hydrochlorothiazide 50 mg, Tid for 6 wk (Nt = 126) + Spironolactone 20 mg, Tid for 6 wk (Nt = 126).
Smith et al²⁰	Acupuncture	CV.12 (Zhongwan), CV.3 (Zhongji), CV.2 (Qugu), LI.15(Jianyu), TE.4 (Yangchi), LU.5 (Chize), LI.4 (Yangxi), ST.36 (Zusanli), SP.9 (Yinlingquan), and SP.6 (Sanyinjiao).	2 × per week for 4 wk, then 1 × per week for 4 wk (Nt = 12)	20 min	Usual care for 8 wk (Nt-UK).
Yao et al²¹	AM	LI.10 (Shousanli), LI.11 (Quchi), LI.14 (Binao), LI.15 (Jianyu), TE.5 (Waiguan), and TE.14 (Jianliao).	Qid lasts 30 d (Nt = 15)	30 min	Diosmin tablets 900 mg, Tid for 30 days (Nt = 90).
Jiao²²	AM	LI.4 (Hegu), TE.5 (Waiguan), GB.21 (Jianjin), LU.1 (Zhongfu), ST.36 (Zusanli), SP.9 (Yinlingquan), LR.3 (Taichong), and Ashi points.	5 × per week for 9 wk (Nt = 45)	20 min	Usual care for 9 wk (Nt-UK).
Zhan and Lou²³	Acupuncture + Functional exercises	CV.12 (Zhongwan), CV.10 (Xiawan), CV.6 (Qihai), CV.4 (Guanyuan), ST.24 (Huaroumen), and ST.26 (Wailing).	Qd for 28 d (Nt = 28)	UK	Functional exercises, 3 to 4 times a week, for 4 wk (Nt = 12-16).
Bao et al¹²	Acupuncture	CV.12 (Zhongwan), CV.3 (Zhongji), TE.14 (Jianliao), LI.15 (Jianyu), LU.5 (Chize), LI.4 (Hegu), ST.36 (Zusanli), and SP.6 (Sanyinjiao).	2 × per week for 6 wk (Nt = 12)	30 min	Wait-list. 2 × per week for 6 wk (Nt = 12).
Wu²⁴	Acupuncture + Functional exercises	CV.12 (Zhongwan), CV.10 (Xiawan), ST.24 (Huaroumen), ST.26 (Wailing), CV.6 (Qihai), and CV.4 (Guanyuan).	Qd for 28 d (Nt = 28)	UK	Functional exercises, 3 to 4 times a week, for 4 wk (Nt = 12-16).
Ba²⁵	AM	LI.14 (Binao), HT.1 (Jiquan), LU.5 (Chize), LI.11 (Quchi), Shousanli (LI.10), TE.5 (Waiguan), LI.4 (Hegu), SP.9 (Yinlingquan), GB.34 (Yanglingquan), ST.36 (Zusanli), SP.6 (Sanyinjiao), and LR.3 (Taichong).	Qid lasts 14 d (Nt = 7)	30 min	Diosmin tablets 450 mg, Bid for 14 d (Nt = 28).
Liu et al²⁶	AM	LI.15 (Jianyu), TE.5 (Waiguan), SP.9 (Yinlingquan), LI.11 (Quchi), CV.9 (Shuifen), and ST.36 (Zusanli).	Qid lasts 28 d (Nt = 14)	30 min	Diosmin tablets 900 mg, Tid for 28 d (Nt = 84).
Liu²⁷	AM + Manual lymphatic drainage	LI.15 (Jianyu), GB.21 (Jianjin), TE.14 (Jianliao), LI.4 (Hegu), TE.5 (Waiguan), LI.11 (Quchi), LU.7 (Lieque), CV.9 (Shuifen), SP.9 (Yinlingquan), and Ashi points.	Qd for 42 d (Nt = 42)	30 min	Manual lymphatic drainage, 10 min at a time, Tid for 42 d (Nt = 126).
Shen²⁸	Moxibustion	LI.14 (Binao), TE.5 (Waiguan), TE.14 (Jianliao), CV.4 (Guanyuan), BL.20 (Pishu), BL.23 (Shenshu), LI.11 (Quchi), and CV.9 (Shuifen).	6 × per month for 2 mo (Nt = 12)	5-15 min	Pneumatic circulation, 30 min at a time, 6 × per month for 2 mo (Nt = 12).
Wang et al²⁹	Moxibustion	LI.14 (Binao), LI.13 (Shouwuli), TE.5 (Waiguan), SI.9 (Jianzhen), BL.23 (Shenshu), and Ashi points.	Qid lasts 28 d (Nt = 14)	30 min	Pneumatic circulation, 30 min at a time, Qid lasts 28 d (14 total).
Zhang et al³⁰	Moxibustion	LI.14 (Binao), LI.11 (Quchi), GV.3 (Yaoyangguan), SI.9 (Jianzhen), and Ashi points.	2 × per week for 4 wk (Nt = 8)	30 min	Pneumatic circulation, 30 min at a time, 2 × per week for 4 wk (Nt = 8).

Abbreviations: AM: acupuncture and moxibustion; Ashi: this refers to an acupuncture point without a specific name or definite location, the site of which is determined aby tenderness or other pathological responses, also called ouch point; Nt: total number of treatments; UK: unknown; Tid: 3 times a day; Qid: once every other day; Qd: once a day; Bid: twice a day.

Risk of Bias

The risk of bias assessment is shown in Figure 2. All the included trials mentioned randomization. Only 2 studies^21,25 did not describe the randomization method in detail, indicating an increased selection bias. Four studies^12,20,28,29 emphasized allocation concealment. Due to the characteristics of AM, it was difficult for the practitioners to incorporate blinding. None of the included studies had a clear description of the blinding of outcome assessments. Nine studies^18,19,21-27 did not report dropouts, and we assessed the risk of attrition bias of these studies as “unclear.” One trial²⁰ did not report all the outcomes mentioned in the published protocols in the results, which could cause a high risk of selective outcome reporting. We found 1 trial¹² at low risk, and all outcomes were presented in a pre-specified way. We assessed the risk of the rest^18,19,21-30 of the studies as “unclear,” because although they appeared to report all outcomes in their Methods section, the protocol was not available.

Figure 2.

Risk of bias. (a) Overall quality assessment. (b) Individual quality assessment.

Changes in Arm Circumference

Effective index for upper limb lymphedema²¹ (%) = upper limb arm circumference before treatment−upper limb arm circumference after treatment/upper limb circumference of the affected arm before treatment−upper limb circumference of the unaffected arm before treatment.

Eleven studies^{12,18,19,22-25,27-30} reported the circumference (cm) of different parts of the affected limb, while 2 studies^21,26 reported the effective index for upper limb lymphedema at 10 cm above the elbow. The results are presented in Table 3.

Table 3.

Comparison of Changes in Arm Circumference Between Acupuncture Group and Control Group.

	Study	Experimental		Control		Heterogeneity		Model	MD (95% CI)	P_o
	Study	Mean	SD	Mean	SD	P	I² (%)	Model	MD (95% CI)	P_o
The mean CM
Moxibustion versus Pneumatic circulation	Wang et al²⁹	24.48	2.02	26.09	1.81	.03	78	RE	−0.66 [−2.63, 1.31]	.51
Moxibustion versus Pneumatic circulation	Zhang et al³⁰	23.47	2.26	23.07	1.42	.03	78	RE	−0.66 [−2.63, 1.31]	.51
The CM at wrist crease
Moxibustion versus Pneumatic circulation	Shen²⁸	16.55	1.47	16.21	0.94	.04	76	RE	−0.20 [−1.25, 0.85]	.71
Moxibustion versus Pneumatic circulation	Wang et al²⁹	16.93	1.28	17.66	1.17	.04	76	RE	−0.20 [−1.25, 0.85]	.71
The CM at the proximal 10 cm of wrist crease
Moxibustion versus Pneumatic circulation	Shen²⁸	23.02	3.17	22.08	3.06	.09	66	RE	−0.17 [−2.13, 1.78]	.86
Moxibustion versus Pneumatic circulation	Wang et al²⁹	22.95	2.75	24.02	1.72	.09	66	RE	−0.17 [−2.13, 1.78]	.86
The CM at the proximal 10 cm of elbow crease
Moxibustion versus Pneumatic circulation	Shen²⁸	31.3	2.89	29.43	2.89	.0002	93	RE	−0.48 [−5.07, 4.12]	.84
Moxibustion versus Pneumatic circulation	Wang et al²⁹	30.77	3.11	33.59	2.73	.0002	93	RE	−0.48 [−5.07, 4.12]	.84
The CM at elbow crease
AM versus Usual care	Zhao et al¹⁸	24	3.2	31	2.8	.43	0	FE	−7.26 [−8.30, −6.21]	<.00001
AM versus Usual care	Jiao²²	24.22	3.03	32.16	2.51	.43	0	FE	−7.26 [−8.30, −6.21]	<.00001
Moxibustion versus Pneumatic circulation	Shen²⁸	27.4	3.14	25.96	2.67	.004	88	RE	−0.24 [−3.44, 2.96]	.88
Moxibustion versus Pneumatic circulation	Wang et al²⁹	27.25	1.92	29.08	2.72	.004	88	RE	−0.24 [−3.44, 2.96]	.88
EIL
AM versus Diosmin	Yao et al²¹	44.71	24.21	17.3	10.13	.97	0	FE	27.68 [24.82, 30.53]	<.00001
AM versus Diosmin	Liu et al²⁶	46.96	7.28	19.27	6.01	.97	0	FE	27.68 [24.82, 30.53]	<.00001

Abbreviations: SD: standard deviation; P and I2: heterogeneity was appraised using the P value alongside the I2 statistic; MD: mean deviation; CI: confidence interval; CM: circumference; FE: fixed-effect model; RE: random-effect model; P_o: test for overall effect; AM: acupuncture and moxibustion; EIL: effective index for upper-limb lymphedema.

Regarding the mean arm circumference^29,30 (the average value of wrist crease, 10 cm proximal to the wrist crease, elbow crease, and 10 cm proximal to the elbow crease) of the affected side, a random effects model was adopted due to high heterogeneity (I^2 =78%, P = .03). Meta-analysis showed no significant difference between the moxibustion and pneumatic circulation groups (MD = −0.66, 95% CI = −2.63 to 1.31, P = .51). Similarly, no difference was observed at the wrist crease, proximal 10 cm of the wrist crease, or 10 cm proximal to the elbow crease.^28,29 However, 2 studies^18,22 that compared AM versus routine care at the elbow crease showed a significant difference (MD = −7.26, 95% CI = −8.30 to −6.21, P < .00001; heterogeneity (I²) = 0%, P = .43). Moreover, no difference was found between moxibustion and pneumatic circulation at the elbow crease.^28,29 The control and intervention groups of the 2 studies^19,25 that were not consistent with the aforementioned studies were not combined for analysis. Four other studies^12,23,24,27 only provided the difference between before and after treatment, but did not provide specific values reflecting the circumference after intervention. Additionally, since the outcomes of the 4 studies did not come from the same location on the affected side, the 4 studies could not be combined with each other. Regarding effective index for upper limb lymphedema, we found that there was a significant difference between the AM group and the oral diosmin tablet group (MD = 24.68, 95% CI = 24.82 to 30.53, P < .00001; heterogeneity (I²) = 0%, P = .97).

Shoulder Joint ROM (in degrees)

Two studies^21,26 reported changes in the ROM of the shoulder in anteflexion, protraction, abduction, adduction, intorsion, and extorsion (Table 4). We observed that AM could improve the ROM in the protraction (MD = 6.77, 95% CI = 2.81-10.73, P = .0008; heterogeneity (I²) = 0%, P = .65), and adduction (MD = 4.17, 95% CI = 1.02-7.32, P = .01; heterogeneity (I²) = 0%, P = .78) directions, but there was no significant difference in ROM for the other directions in the control group. In addition, both control groups were treated with oral diosmin tablets.

Table 4.

Comparison of Shoulder Joint ROM Between AM Group and Oral Diosmin Tablets Group.

Study	Experimental		Control		Heterogeneity		Model	MD (95% CI)	P_o
Study	Mean	SD	Mean	SD	P	I² (%)	Model	MD (95% CI)	P_o
Protraction
Yao et al²¹	95.46	8.06	89.58	7.3	.65	0	FE	6.77 [2.81, 10.73]	.0008
Liu et al²⁶	96.07	13.06	88.35	12.93	.65	0	FE	6.77 [2.81, 10.73]	.0008
Adduction
Yao et al²¹	93.98	7.16	90.27	5.47	.78	0	FE	4.17 [1.02, 7.32]	.01
Liu et al²⁶	94.99	10.01	90.4	9.91	.78	0	FE	4.17 [1.02, 7.32]	.01
Anteflexion
Yao et al²¹	95.26	6.45	95.11	4.86	.87	0	FE	0.31 [–3.27, 3.89]	.87
Liu et al²⁶	96.81	16.89	95.97	17.08	.87	0	FE	0.31 [–3.27, 3.89]	.87
Abduction
Yao et al²¹	96.62	3.29	96.17	4.19	.29	11	FE	1.16 [–1.20, 3.52]	.34
Liu et al²⁶	96.88	12.09	93.41	10.07	.29	11	FE	1.16 [–1.20, 3.52]	.34
Intorsion
Yao et al²¹	98.6	0.9	98.6	1.86	.05	75	RE	2.06 [–3.06, 7.19]	.43
Liu et al²⁶	99.86	13.07	94.49	10.34	.05	75	RE	2.06 [–3.06, 7.19]	.43
Extorsion
Yao et al²¹	98.7	1.27	99.34	0.99	.02	83	RE	2.30 [–4.50, 9.11]	.51
Liu et al²⁶	96.82	14.01	90.42	11.68	.02	83	RE	2.30 [–4.50, 9.11]	.51

Abbreviations: SD: standard deviation; P and I2: heterogeneity was appraised using the P value alongside the I2 statistic; MD: mean deviation; CI: confidence interval; FE: fixed-effect model; RE: random-effect model; P_o: test for overall effect.

VAS

The results of 2 studies^23,24 showed that acupuncture could significantly reduce the patients’ VAS for pain (MD = −1.33, 95% CI = −1.52 to −1.15, P < .00001; heterogeneity (I²) = 0%, P = .57). In addition, the intervention in the control group of both the studies included functional exercises, while the intervention in the experimental group involved acupuncture treatment based on functional exercises.

Three studies^28-30 reported the VAS for swelling. Three studies on the effects of moxibustion versus pneumatic circulation showed a significant difference (MD = −0.51, 95% CI = −0.85 to −0.17, P = .003; heterogeneity (I²) = 0%, P = .96) (Figure 3).

Figure 3.

Forest plots of VAS.

Bioimpedance and Quality of Life

Bioimpedance was mentioned as an outcome indicator in 2 studies.^12,20 However, 1 study²⁰ reflected the change in bioimpedance, while another¹² showed the specific values before and after treatment; therefore, the results were not combined.

Although 5 studies^21,26-28,30 showed that AM could significantly improve the quality of life, the assessment scales they used were not uniform. One study²⁸ used the scale developed by the European Organization for Research and Treatment, 1 study²¹ used a Likert scale, 1 applied³⁰ the scale that is generally used for Chinese cancer patients, and the remaining 2 studies^26,27 did not mention specific scales.

AE

Four studies^12,20,25,28 have reported the AEs of AM in detail. The AE report showed that some participants had local symptoms; bruises (45 cases) were the most common, followed by discomfort (3 cases), hematoma (2 cases), pain (2 cases), burns (2 cases), severe swelling (1 case), cough (1 case), and skin infection (1 case).

Follow-up

Among the 4 studies^12,20,28,29 that referred to the follow-up, the study by Smith et al.²⁰ explained that the 3 months follow-up data was not provided in the article as the staff did not have the resources to perform final measurements for the participants. Bao et al.¹² found that the size of the affected arm increased by nearly 10% compared with the unaffected arm, 3 months after treatment and not immediately after treatment. Wang et al.²⁹ and Shen²⁸ found that 1 month after the end of treatment, some patients’ limbs began to show varying degrees of swelling.

Discussion

Main Findings

Our results showed that AM reduced the circumference at the elbow crease more than other treatments, but no difference was found at other measurement points (wrist crease, 10 cm proximal to the wrist crease, and 10 cm proximal to the elbow crease). This finding is also supported by the results shown in the summary statistics in our study; LI.11, an acupoint located on the elbow crease, was selected for physical stimulation in most trials. This indicates that appropriate acupoint selection can have a better curative effect locally on the affected limb. Anatomically, the elbow joint, connecting the upper arm and forearm, is composed of the lower end of the humerus, the upper end of the ulna, and the upper end of the radius. In daily life, compared to most other joints, the elbow joint is always in a state of frequent and large arc movements.³¹ Therefore, reducing the degree of edema at the elbow joint and allowing the elbow joint to recover is very important for patients with BCRL. In this respect, AM may have an advantage over routine care.

Regarding effective index for upper limb lymphedema and shoulder joint ROM, the results of the RCTs by Yao C and Liu Xiaofang were combined for analysis. Although only 2 studies could be analyzed, the same experimental group and control group minimized confounding factors, which gave the results a certain degree of credibility. In the case of oral diosmin, the tablets are first hydrolyzed into geraniol by the action of intestinal flora, which then enter the systemic circulation. However, AM is an invasive treatment that directly acts on the lesion, especially when the Ashi points (acupoints without a specific name or an exact location; the location is reflected by tenderness or other pathological reactions, also called tender points) are selected. This may explain, at least in part, why AM may improve the effective index for upper limb lymphedema and ROM of the shoulder joint more than diosmin tablets.

With regard to AM lowering the VAS pain scores in patients with BCRL, it is worth noting that previous studies^32,33 have also shown that AM is effective in the treatment of chronic pain. In addition to clinical reports, Yu et al.³⁴ proposed that the cause of pain relief by acupuncture may be related to the increased connectivity between the precentral gyrus and middle frontal gyrus. However, in the present meta-analysis, this conclusion should be considered with caution. Because the experimental group (acupuncture and functional exercises) included in the study added acupuncture to the control group (functional exercises), we cannot completely rule out that the synergistic effect of the combined treatment exceeds the sum of the 2 separate treatments.

Unlike the VAS score for pain, the conclusion regarding the VAS score for swelling is definitive; moxibustion may lower patients’ VAS scores for swelling than pneumatic circulation. Pneumatic circulation is achieved with mechanical compression equipment or intermittent pneumatic compression equipment, which is used to apply pressure to the affected limb to improve blood and lymphatic circulation. Moxibustion, as a warm stimulation, can dilate blood vessels, increase blood flow, and improve microcirculation. In addition, moxibustion provides warm stimulation suitable for the human body, so that the patient has a pleasant emotional experience and a healthier psychological state. Therefore, considering that both interventions can improve circulation, moxibustion may be more effective than pneumatic circulation based on the VAS score for swelling obtained by the patient’s own subjective feelings.

This meta-analysis revealed that AM may cause discomfort, bruises, hematoma, pain, skin infection, burning, severe swelling, and coughing. However, AEs were mostly grade I or II, and no grade IV AEs were observed. After timely and effective treatment, no serious complications occurred. The participants were able to tolerate the treatment, and there were no treatment-related deaths. Finally, the 1 to 3 months follow-up survey of 3 RCTs indicated that lymphedema in some patients had recurred; therefore, there is no evidence to confirm that AM has a sustained effect on BCRL.

Strengths and Limitations

To our knowledge, this is the latest and most comprehensive meta-analysis summarizing the results regarding the effects and safety of AM for BCRL. This review conducted a meta-analysis based on different control methods to avoid clinical heterogeneity of samples that may affect the results of the study. In contrast to previous meta-analyses,^9,10,35,36 strict filtering criteria were implemented for the studies included in this review. For the included RCTs, the intervention group had to be ordinary acupuncture and/or ordinary moxibustion, in order to eliminate the effects of other measures (such as electroacupuncture, laser, traditional Chinese medicine, massage, and cupping, among others) to the extent possible. Furthermore, to obtain more definitive conclusions, we discussed acupuncture and moxibustion separately.

This study has some limitations. First, most of the included articles were of poor quality. Several studies lacked details of allocation concealment, and none of the articles mentioned blinding to the outcome assessors. Second, the analysis was based on small sample sizes, so the results should be interpreted carefully. Third, we cannot fully exclude the effect of AM manipulation on the study outcomes. Finally, although we differentiated acupuncture and moxibustion, we did not further compare their efficacy or study the synergistic effects of acupuncture and moxibustion due to the small number of included studies.

Future Perspectives

The selection and combination of acupoints play an important role in the effectiveness of treatments. For BCRL, all trials focused on local acupoints on the upper limbs. These findings are consistent with those of previous studies.³⁶ However, the mechanism of specific acupoint stimulation and acupoint combination requires further study. Moreover, different studies measured the circumference of the affected limb at different positions as outcome indicators, which made it difficult to aggregate analyses. In future trials, it may be a better option to report the changes in the circumference of the upper limbs at 4 positions (wrist crease, 10 cm proximal to the wrist crease, elbow crease, and 10 cm proximal to the elbow crease) at the same time. Finally, since the efficacy of the different control groups is still uncertain, we suggest that in future studies, pneumatic circulation or routine care could be used for comparison in addition to waiting lists or sham acupuncture control.

Conclusion

Overall, our study results further clarify that AM has a certain efficacy in the treatment of BCRL. AM may reduce arm circumference at the elbow crease (compared to routine care), increase effective index for upper limb lymphedema (compared to oral diosmin tablets), improve shoulder joint ROM in the protraction and adduction directions (compared to oral diosmin tablets), reduce VAS for swelling (compared to pneumatic circulation), and decrease VAS for pain (compared to blank control). Although AM demonstrates more advantages than the other therapies, more compelling evidence is essential to confirm the benefits of AM.

Supplemental Material

sj-pdf-1-ict-10.1177_15347354211044107 – Supplemental material for Effects of Acupuncture and Moxibustion on Breast Cancer-Related Lymphedema: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Supplemental material, sj-pdf-1-ict-10.1177_15347354211044107 for Effects of Acupuncture and Moxibustion on Breast Cancer-Related Lymphedema: A Systematic Review and Meta-Analysis of Randomized Controlled Trials by Yu Gao, Tingting Ma, Mei Han, Mingwei Yu, Xiuhui Wang, Yiren Lv and Xiaomin Wang in Integrative Cancer Therapies

Footnotes

Acknowledgements

The authors would like to thank Ling Wang for excellent technical support.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by a grant (No. Z191100008319006) from Beijing Science and Technology Plan Project.

ORCID iD

Xiaomin Wang

Supplemental Material

Supplemental material for this article is available online.

References

Miller

Nogueira

Mariotto

, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019;69:363-385.

Siegel

Miller

Jemal

Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7-30.

Invernizzi

Michelotti

Noale

, et al. Breast cancer systemic treatments and upper limb lymphedema: a risk-assessment platform encompassing tumor-specific pathological features reveals the potential role of Trastuzumab. J Clin Med. 2019;8:138.

Runowicz

Leach

Henry

, et al. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. CA Cancer J Clin. 2016;66:43-73.

Omidi

Kheirkhah

Abolghasemi

Haghighat

Effect of lymphedema self-management group-based education compared with social network-based education on quality of life and fear of cancer recurrence in women with breast cancer: a randomized controlled clinical trial. Qual Life Res. 2020;29(7):1789-1800.

Cal

Bahar

Women’s barriers to prevention of lymphedema after breast surgery and home care needs: a qualitative study. Cancer Nurs. 2016;39:E17-e25.

Stuiver

Ten Tusscher

McNeely

ML.

Which are the best conservative interventions for lymphoedema after breast cancer surgery?

BMJ. 2017;357:j2330.

Cassileth

Van Zee

Yeung

, et al. Acupuncture in the treatment of upper-limb lymphedema: results of a pilot study. Cancer. 2013;119:2455-2461.

Zhu

Xie

, et al. Effects of acupuncture on breast cancer-related lymphoedema: a systematic review and meta-analysis. Explore. 2020;16:97-102.

10.

Zhang

Wang

Zhang

Yang

Liu

Effects of acupuncture on breast cancer-related lymphoedema: a systematic review and meta-analysis of randomised controlled trials. Acupunct Med. 2019;37:16-24.

11.

Chien

Liu

Fang

CJ.

The effect of acupuncture in Breast Cancer-Related Lymphoedema (BCRL): a systematic review and meta-analysis. Integr Cancer Ther. 2019;18:1534735419866910.

12.

Bao

Iris Zhi

Vertosick

, et al. Acupuncture for breast cancer-related lymphedema: a randomized controlled trial. Breast Cancer Res Treat. 2018;170:77-87.

13.

Higgins

JPT

Altman

Gotzsche

, et al. The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928-d5928.

14.

Higgins

Thompson

Deeks

Altman

DG.

Measuring inconsistency in meta-analyses. BMJ. 2003;327:557-560.

15.

Begg

Mazumdar

Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088-1101.

16.

Egger

Davey Smith

Schneider

Minder

Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629-634.

17.

Moher

Liberati

Tetzlaff

Altman

; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.

18.

Zhao

Wang

YZ.

Observation on therapeutic effect of acupuncture on upper limb lymphedema after breast cancer operation. Chin J Clin Res. 2012;25:918-919.

19.

Huang

Wei

, et al. Observation on therapeutic effect of acupuncture on lymphedema of upper limbs after breast cancer operation. Chekiang J Tradit Chin Med. 2014;49:59.

20.

Smith

Pirotta

Kilbreath

A feasibility study to examine the role of acupuncture to reduce symptoms of lymphoedema after breast cancer: a randomised controlled trial. Acupunct Med. 2014;32:387-393.

21.

Yao

Chen

, et al. Effects of warm acupuncture on breast cancer-related chronic lymphedema: a randomized controlled trial. Curr Oncol. 2016;23:e27-e34.

22.

Jiao

HF.

Evaluation of curative effect of acupuncture on upper limb lymphedema after breast cancer surgery. Nei Mongol J Tradit Chin Med. 2017;130:23-24.

23.

Zhan

Lou

CS.

Clinical observation of abdominal acupuncture combining with upper limb functional exercise in treatment of patients with breast cancer-related upper limb lymphoedema. Chin J Woman Child Health Res. 2017;28:570-572.

24.

Analysis of the effect of abdominal acupuncture combined with upper limb functional exercise on upper limb lymphedema after breast cancer surgery. Chin Med J Metall Ind. 2018;35:324-325.

25.

Clinical Observation on Warm Acupuncture Treatment of Breast Cancer Related Lymphedema. Shanxi University of Chinese Medicine; 2019.

26.

Liu

Zhang

Kong

Observational study on the efficacy of needle warming moxibustion in edema of the upper extremity and anxiety-depression of mammary cancer patients after operation. World Chin Med. 2019;14:1856-1860.

27.

Liu

YN.

Clinical observation of warm needling for upper-limb lymphedema after breast cancer surgery. Shanghai J Acupunct Moxibustion. 2019;38:634-637.

28.

Shen

Study on the Evaluation of the Efficacy of Yaoai and Qingai in the Treatment of Upper Limb Lymphedema After Breast Cancer Operation Based on the Theory of Circalunar Rhythm. Beijing University of Chinese Medicine; 2019.

29.

Wang

Yang

Fan

Pei

Moxibustion as a therapy for breast cancer-related lymphedema in female adults: a preliminary randomized controlled trial. Integr Cancer Ther. 2019;18:1534735419866919.

30.

Zhang

Yang

Pei

, et al. Clinical observation of mild moxibustion in the treatment of breast cancer related lymphedema. World J Integr Tradit West Med. 2020;15:1934-1937.

31.

Crawford

Varghese

Mani

Neff

JR.

Heterotopic ossification: are range of motion exercises contraindicated?

J Burn Care Rehabil. 1986;7:323-327.

32.

Yang

Chen

, et al. Moxibustion for pain relief in patients with primary dysmenorrhea: a randomized controlled trial. PLoS One. 2017;12:e0170952.

33.

White

Foster

Cummings

Barlas

Acupuncture treatment for chronic knee pain: a systematic review. Rheumatology. 2007;46:384-390.

34.

Lin

S-H

Tsai

C-C

, et al. Acupuncture effect and mechanism for treating pain in patients with Parkinson’s disease. Front Neurol. 2019;10:1114-1114.

35.

Jin

Xiang

Feng

, et al. Effectiveness and safety of acupuncture moxibustion therapy used in breast cancer-related lymphedema: a systematic review and meta-analysis. Evid Based Complement Alternat Med. Published online May 11, 2020. doi:10.1155/2020/3237451

36.

Hou

Pei

Song

, et al. Acupuncture therapy for breast cancer-related lymphedema: a systematic review and meta-analysis. J Obstet Gynaecol Res. 2019;45:2307-2317.