Acupuncture for treatment-related side effects in women with breast cancer

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess:

  • the effectiveness of acupuncture in alleviating the side effects of chemotherapy, radiotherapy, surgery, hormonal therapy or palliative treatment in women with breast cancer; and

  • the safety of acupuncture.

Background

Description of the condition

Breast cancer is the most common cancer and leading cause of cancer death amongst women worldwide, both in developed and developing countries (WHO 2011). In 2008, it accounted for 23% (1.38 million) of total new cancer cases and 14% (458,400) of total cancer deaths (Jemal 2011).

Varying incidence rates result largely from differences in reproductive and hormonal factors and the availability of early detection facilities (Jemal 2010). Standard treatment options for breast cancer include surgical interventions, chemotherapy, radiotherapy and endocrine therapy. In spite of the major attributes of standard therapies, patients suffer from severe side effects and psychological distress during adjuvant therapy (Markes 2006) and even after cessation of therapy.

Side effects differ depending on the mode of treatment. Surgery or radiation treatment is usually a primary cause of lymphoedema (Shapiro 2001) and post-mastectomy pain is also a common side effect. Radiotherapy causes short-term side effects such as fatigue and skin erythema and long-term side effects including lymphoedema, cardiac and pulmonary toxicities, brachial plexopathy and secondary cancer (Shapiro 2001; Truong 2004). Cytotoxic chemotherapy is also known to have substantial short- and long-term side effects (Partridge 2001). Short-term side effects occur during the course of treatment and are usually resolved within months of completion of the treatment (Zhang 2007). These include fatigue, emesis (vomiting), stomatitis, alopecia (loss of hair), temporary ovarian failure, depression, myelosuppression (bone marrow suppression), thromboembolism (blood clot inside of the vessel), myalgias (pain in the muscles) and neuropathy (pain and numbness in the limbs when the peripheral nervous system (outside of the brain and spinal cord) is damaged) (Frisk 2011; Markes 2006; Shapiro 2001). Long-term side effects often have a much later onset and may last for many years (Ramalingam 2002). These include permanent premature ovarian failure in premenopausal patients, weight gain, cardiac dysfunction, leukaemia and potential cognitive impairment (Ramalingam 2002; Shapiro 2001).   

Endocrine treatment (e.g. tamoxifen or aromatase inhibitors) contributes to symptoms secondary to oestrogen withdrawal, the most common of which are vasomotor symptoms including hot flushes and night sweats. Breast cancer survivors generally experience vasomotor symptoms to a greater degree and they are often more distressing and of greater duration (Carpenter 2002) than women going through 'natural' menopause. The recommended duration for endocrine treatment is usually five years, however the side effects may lead to patients discontinuing potentially life-saving adjuvant treatment (Gibson 2009; Loibl 2011).

Description of the intervention

Both pharmacological and non-pharmacological interventions have been used to alleviate the side effects of treatments for breast cancer (Boardman 2012; Markes 2006; Zhang 2007). However, the clinical benefits of pharmacological interventions for managing the side effects of oncological therapies can be very limited since they can also produce secondary side effects themselves. For example, the administration of oestrogen to women with breast cancer for relieving menopausal symptoms and preventing osteoporosis (in the long term) is controversial, because it may contribute to an increased risk of breast cancer or even a new development of primary breast cancer (Shapiro 2001). Many women do not wish to experience further side effects caused by pharmacological agents, or want to take medication additional to their standard therapies (de Valois 2010).  

Non-pharmacological interventions to manage treatment side effects appear to be preferred, and the use of complementary and alternative medicine (CAM) has been increasing amongst patients with cancer in recent decades (Cassileth 2001; Lu 2009). It has been reported that women with breast cancer are more likely to use CAM (Molassiotis 2005; Patternson 2002); this may be as high as 53% (Lewith 2002) to 87% (Kremser 2008), and they are more likely to use acupuncture (Chao 2009). This echoes an overall tendency: the steadily growing popularity of acupuncture in many Western nations (Hamilton 2008; Harkin 2007; Hope-Allan 2004; Schmincke 2008; Zhu 2009).

Acupuncture involves the insertion of fine, single-use, sterile needles in acupuncture points (or acupoints) according to traditional Chinese medicine (TCM) theory. The common forms of acupuncture include body acupuncture, auricular acupuncture and scalp acupuncture according to anatomical regions, and the methods of manipulation may differ from manual to electroacupuncture (Qiu 1993).

With respect to safety, acupuncture appears to have a favourable safety profile if it is performed by a qualified and experienced practitioner (NCCAM 2006). One large study reported only 43 minor adverse events (such as nausea, dizziness, heavy sweating, mild bruising, pain and bleeding) associated with 34,407 treatments and no serious adverse events (MacPherson 2001).

How the intervention might work

How acupuncture works to eliminate the side effects of cancer treatments for breast cancer is still unknown, however emerging literature suggests acupuncture might work through several pathways. For example, acupuncture may induce body signals that are transmitted to the central nervous system (CNS), which in turn activates anti-inflammatory signals and pain relief processes through both humoral and neural mechanisms (Cho 2006; Sekido 2003). This sheds some light on how side effects can be plausibly managed by acupuncture.

Since the 1970s, it has been established that acupuncture may influence pain mediators through the release of neurotransmitters, such as ß-endorphin and endogenous opioids in the CNS (Cabýoglu 2006; Lin 2008; Ma 2004). The endogenous opioid-mediated mechanisms of acupuncture seem to be well understood (Han 2004).

It has been suggested that acupuncture initiates anti-inflammatory pathways in addition to opoid-mediated pathways. Animal studies have demonstrated that electroacupuncture may induce anti-inflammatory properties at both peripheral and central pain (i.e. nociceptives) sites (Lee 2006; Moon 2007). Prostaglandin E2 produced in the local inflammatory site is essential in initiating and maintaining inflammatory hyperalgesia (Shahed 2001). Clinical research has shown that electroacupuncture therapy seems to have a pain relief effect which might be associated with decreased measures of prostaglandin E2 in urine samples (Lee 2009).

Immune functions may also be involved when using acupuncture. Some animal studies have shown that bilateral electroacupuncture stimulation (at acupuncture point ST36) for three consecutive days enhances splenic natural killer (NK) cell activity (Yu 1998), while acupuncture (at BL23 points) for 20 days increases the ratio of NK cells to T lymphocytes in the spleen of mice after day seven (Okumura 1999).

A Japanese study suggested that acupuncture influenced the immune system through leukocyte and lymphocyte subpopulations in human peripheral blood (Takahashi 2009). In addition, a Chinese study showed that patients assigned to adjuvant electroacupuncture with chemotherapy had no significant changes in their T cell subpopulations, NK activity, immunoglobulin and leukocyte counts at the end of the fourth course of chemotherapy, in comparison with those who had chemotherapy without electroacupuncture in a control group (Ye 2004). This adds value in supporting the hypothesis that electroacupuncture might minimise the potential side effects of chemotherapy.

Studies have shown that the attributive effects of acupuncture are comprehensive, spanning from modulating an immunosuppressed or immunoactivated condition through the immune system to having an impact on the CNS (Lewith 2005; Ma 2004).

Why it is important to do this review

Improvements in early diagnosis and treatment have increased the life expectancy of women with breast cancer. In turn, this has led to specific problems being encountered by long-term breast cancer survivors. There has been a shift of emphasis to focusing on the negative impact of treatment on patients' quality of life, especially from long-term side effects (Pinto 2011), as well as the increased use of healthcare resources (Loibl 2011).

The use of CAM amongst cancer patients or survivors is due to the desire to increase the body’s ability to fight cancer or improve physical and emotional well-being (Molassiotis 2005). An Australian survey on women with breast cancer reported that: "common reasons for use included improving physical (86.3%) and emotional (83.2%) well-being and boosting the immune system (68.8%)" with 49.2% specifically reporting to "reduce treatment side effects" (Kremser 2008). Another large survey stated that acupuncture was effective (40%) or very effective (7.7%) for modulating immune functions, relieving pain, alleviating menopausal symptoms or managing other discomforts in the breast cancer population (Cui 2004). However, there has been a lack of scientific evidence to support these claims or empirical experience reported by patients or survivors.

Furthermore, despite the popularity of acupuncture in cancer patients (de Valois 2010; Frisk 2011; Hervik 2010; Lu 2009; Shen 2000; Sima 2009), acupuncture has not met with wide approval amongst medical professionals and there has been poor communication between patients and medical carers (Lu 2009; Molassiotis 2005). Patients and healthcare professionals need more information on the effectiveness and safety of complementary medicine interventions.

A few systematic reviews on the role of acupuncture in managing side effects in women with breast cancer have been previously conducted (Chao 2009; Ezzo 2006; Lee 2009a). However, some reviews focused on specific symptoms and there was a lack of consideration of the unique features of TCM philosophy that underpin acupuncture, when the tools of evidence-based practice were applied to assess its effectiveness.

It has been suggested that acupuncture as a treatment to control side effects may potentially alleviate conventional therapy-induced side effects and improve quality of life (Price 2012).

Objectives

To assess:

  • the effectiveness of acupuncture in alleviating the side effects of chemotherapy, radiotherapy, surgery, hormonal therapy or palliative treatment in women with breast cancer; and

  • the safety of acupuncture.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomised controlled trials (RCTs) of acupuncture used to treat side effects in women with breast cancer. We will verify the status of RCTs by contacting the authors of primary studies. We will include cross-over trials if the number of participants going from acupuncture to control are the same as from control to acupuncture, and if pre-cross-over data are available.

We will exclude quasi-randomised trials.

We will make no restrictions regarding year and language of publication.

Types of participants

Women of any age (> 18 years old), diagnosed with breast cancer regardless of tumour type, stage (stage I-III according to TNM Classification of Malignant Tumours by the International Union Against Cancer and American Joint Committee on Cancer (AJCC) Stage Grouping designated by the AJCC (Woodward 2003)) and type of cancer treatment (chemotherapy, radiotherapy, surgery, endocrine therapy or palliative treatment), experiencing treatment-induced side effects.

Participants can be actively receiving treatment, in long-term follow-up or receiving palliative care.

Types of interventions

Interventions will include: (a) body acupuncture with needle insertion at traditional acupuncture points or insertion at non-traditional points, also called 'Ashi' or tender areas, (b) scalp or auricular acupuncture and (c) electroacupuncture.

The intervention may be used alone or as an adjunct to other methods (if the control group also received the same concomitant treatment as the acupuncture group). 

The source of stimulation could be hand, moxibustion with a warming needle or electrical.

We will exclude acupuncture studies that solely involve laser acupuncture, acupressure, moxibustion (other than a warming needle method), point injection, blood letting tap pricking or cupping on pricked superficial blood vessels.

Control interventions will include: (a) a placebo, also called sham acupuncture (with the use of a non-penetrating needle) or non-traditional acupuncture points that are not tender to touch and are located in the vicinity of traditional acupuncture points, (b) conventional biomedical treatment and (c) no treatment at all.

We will exclude trials only comparing different acupuncture treatments.

Types of outcome measures

Primary outcomes
  • The incidence and severity of chemotherapy, radiotherapy, hormonal therapy or palliative treatment-related toxicities if they were reported according to internationally accepted criteria for common toxicities (e.g. World Health Organization (WHO), Eastern Cooperative Oncology Group (ECOG) or National Institutes of Health (NIH) criteria for adverse effects), as measured by a validated instrument/tool (e.g. clinical manifestations or biomarkers) 

  • The incidence and severity of nausea and vomiting, lymphoedema, vasomotor symptoms and post-mastectomy pain following surgical treatment

Secondary outcomes
  • Patient-reported physical and psychological indices of symptom distress (measured using reliable and valid assessment tools)

  • Quality of life, as measured by a validated instrument (not limited to the European Organisation for Research on Treatment of Cancer (EORTC) QLQ-C30 (Aaronson 1993) and the SF-36 or the Rotterdam Symptom Checklist (Watson 1992))

  • Changes in outcomes as measured by TCM diagnostic tools

  • Incidence and type of side effects of acupuncture

Search methods for identification of studies

Electronic searches

We will search the following databases with key words such as breast cancer, side effect, adverse effect and acupuncture.

  • The Cochrane Breast Cancer Group's (CBCG's) Specialised Register. The CBCG will search their Specialised Register. Details of the search strategies used by the Group for the identification of studies and the procedure used to code references are outlined in the Group's module (CBCG 2012). We will extract trials coded with the key words 'breast cancer', 'early breast cancer', 'locally advanced breast cancer', 'advanced breast cancer', 'palliative', 'alternative/complementary intervention', 'side effect', 'treatment induced side effect', 'distress syndrome', 'psychological distress', 'adverse effect', 'side effect symptom', 'adverse effect symptom', 'toxic symptom', 'toxicity', 'nausea', 'vomit', 'hot flash', 'hot flush', 'night sweat', 'night time awakening', 'sleep disturbance', 'psychological symptom', 'lymphedema', 'lymphoedema', 'post-mastectomy pain', 'acupuncture', 'acupuncture therapy', 'traditional Chinese medicine', 'TCM', 'scalp acupuncture', 'auricular acupuncture', 'warming needle', 'moxibustion', 'electrical stimulation' and 'electroacupuncture' for consideration.

  • MEDLINE and EMBASE (via Embase.com) (until search date). See Appendix 1.

  • The WHO International Clinical Trials Registry Platform (ICTRP) search portal (http://apps.who.int/trialsearch/Default.aspx) for all prospectively registered and ongoing trials. See Appendix 2.

  • Clinicaltrials.gov (http://clinicaltrials.gov/ct2/search). See Appendix 3.

  • We will also search one of electronic Chinese databases: the China National Knowledge Infrastructure (CNKI, from 2000 until search date). See Appendix 4.

We will ask for the assistance of the Trials Search Co-ordinator of the CBCG for database searches.

Searching other resources

We will also check citation lists of included trials, eligible studies and relevant review articles. We will also undertake personal communication with manufacturers, experts and specialists in the field.

Data collection and analysis

Selection of studies

Two review authors (XZ and WL) will undertake the study selection. XZ and WL will screen the titles and abstracts of articles found in the search and discard studies that are clearly ineligible, but they will aim to be overly inclusive rather than risk losing relevant studies. XZ will obtain copies of the full-text articles and make copies for WL in which details of the authors and institutions have been struck out and the results section removed. Both review authors will independently assess whether the studies meet the inclusion criteria, with discrepancies regarding eligibility to be resolved by discussion within the author group (AB, EM and HC).

We will seek further information from the trial authors where papers contain insufficient information to make a decision about eligibility. We will record details of excluded studies in the 'Characteristics of excluded studies' table.

Since both XZ and WL are bilingual in English and Chinese, there will be no need to run full English translations during the screening process. However, English translations may be provided if disagreements occur. There will be no language restriction, hence we will seek other language translations as required.

Data extraction and management

XZ and WL will independently extract data using data extraction forms as outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). This will include assessing study characteristics such as methods, participants, interventions and outcomes.

Based on a pre-designed data extraction form, XZ and WL will also independently evaluate the methodological quality of the selected studies to assess the extent to which trial design, data collection and statistical analysis reduced or avoided bias based on the extraction form. Discrepancies will be resolved within the group by discussion. 

XZ will independently enter data into the Review Manager software (RevMan) but WL will check to prevent transcription errors.

For studies where there are more than one publication, we will use only the most recent publication as the primary reference and extract data from all of the publications.

We will contact either the first or corresponding trial author to clarify data extraction issues.

Assessment of risk of bias in included studies

Three review authors (XZ, EM and WL) will independently critically assess the risk of bias of the included studies in this review using a domain-based evaluation that includes the following domains: sequence generation, allocation concealment, blinding, incomplete data assessment, selective outcome reporting and other source of bias (in accordance with the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 (Higgins 2011)).

The review authors' assessments for each domain will be entered into a 'Risk of bias' table and classified as either 'low risk', 'high risk' or 'unclear' risk (Higgins 2011).

We will contact all study contact authors by mail or email to confirm that trials were randomised and meet our inclusion criteria. If we are unable to contact the authors, the study will be excluded unless randomisation can otherwise be confirmed.

Any disagreement will be resolved by discussion within the author review group.

Measures of treatment effect

We will perform statistical analysis in accordance with the guidelines outlined in the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 (Higgins 2011).

Dichotomous data

We will use discrete events such as the number of participants reporting nausea or pain to calculate the absolute risk reduction (ARR, also known as risk difference). When a statistically significant ARR exists between interventions, we will derive the number needed to treat to benefit (NNTB) or harm (NNTH) along with 95% confidence intervals (CIs). We will also present dichotomous outcomes in terms of both raw numbers and percentages of participants in each study arm benefiting from therapy or suffering adverse events.

Continuous data

For continuous outcome data (e.g. quality of life), we will express results from each study as a mean difference (MD) with 95% CIs. It is anticipated that different scales may be used to report the same outcomes (e.g. hot flushes) and, in this case, we will use the standardised mean difference (SMD).

Our primary analysis will employ a random-effects model, with sensitivity analysis using a fixed-effect model, using Review Manager software (RevMan).

Unit of analysis issues

We will analyse dichotomous outcomes as per woman randomised (e.g. number of women with an adverse effect/total number of women randomised). When data are presented in a continuous form we will treat the data so that participants from individual trials are included only once in each comparison. Only first-phase data from cross-over trials will be included.

Dealing with missing data

We will contact all study authors by phone or email to obtain any missing patient data. We will record the date of contact. If we are unable to obtain missing data, analyses will be based on patient populations in which outcomes were reported.

We will note discrepancies between the number of patients enrolled and number of patients in whom outcomes were reported in the 'Characteristics of included studies' table. Where studies report statistics based on intention-to-treat (ITT) or modified ITT populations, we will perform available case analyses (Higgins 2011).

We will discuss the impact of missing data in the 'Discussion' section of the review.

Assessment of heterogeneity

We will visually inspect forest plots as an informal assessment of heterogeneity and will quantify statistical heterogeneity using the I2 statistic. The I2 statistic is useful to quantify inconsistency among results of included studies in a meta-analysis, since it has an intuitive interpretation and is specifically designed to be independent of the number of included trials. The I2 is interpreted to be the proportion of total variation in study estimates that is due to heterogeneity rather than sampling error. We will consider an I2 value of greater than 50% to indicate substantial heterogeneity (Higgins 2011). Where possible, we will perform predetermined sub-analyses or sensitivity analyses in an attempt to explain heterogeneity.

If visual inspection of forest plots suggests that results are consistent and the corresponding I2 value is low, we will use a fixed-effect model. Otherwise, we will combine results using a random-effects model. We will report 95% confidence intervals alongside I2 values and report between-study variance to reflect uncertainty in the estimate. 

Assessment of reporting biases

We will make no attempt to assess reporting bias in RCTs. We aim to minimise the potential impact of reporting bias by ensuring a comprehensive search for eligible studies, including the WHO ICTRP and by being alert to the duplication of data.

If there are 10 or more studies in an analysis, we will use a funnel plot to explore the possibility of small study effects (a tendency for estimates of the intervention effect to be more beneficial in smaller studies).

Data synthesis

We will combine the data from primary studies when they are sufficiently similar using a random-effects model. For dichotomous outcomes, we will use the Mantel-Haenszel method. For continuous outcomes, we will use the inverse-variance method.

We will also consider looking at the different endpoints of each comparison, such as acupuncture during cancer treatment, acupuncture in between sessions of treatment (e.g. radiotherapy or chemotherapy) or acupuncture after treatment.

We will display an increase or decrease in the risk of a particular outcome, which may be beneficial or detrimental, graphically in the meta-analyses. We will display an increase in the risk of an outcome to the right of the centre line and a decrease in the risk of an outcome to the left of the centre line.

In the event of substantial clinical, methodological or statistical heterogeneity we will not combine study results by means of meta-analysis, but instead summarise them in narrative form.

Subgroup analysis and investigation of heterogeneity

Where data are available, we will conduct subgroup analyses to assess heterogeneity and to determine the effect of different types of acupuncture therapies, such as manual acupuncture, electroacupuncture and acupuncture with moxibustion. We will also consider subgroup analysis on different outcome types such as vomiting and nausea, hair loss, lymphoedema etc. Where heterogeneity exists, we will investigate potential causes such as differences between control interventions, outcome types, participant characteristics and study design.

Sensitivity analysis

We will undertake sensitivity analysis to examine the robustness of the results in relation to a number of factors relating to the way the study was performed.

  1. Excluding studies based on the 'Risk of bias' assessment, e.g. those of the lowest grade of allocation quality and then again for studies rated with poor allocation quality (i.e. excluding studies using quasi-randomisation or without adequate safeguards for allocation concealment).

  2. Excluding studies of poor overall methodological quality. We will consider the following aspects of quality for this sensitivity analysis separately: inadequate blinding, no stated method of diagnosis, incomparable groups (either because they have different baseline characteristics or because they do not have identical care programmes), no intention-to-treat analysis.

  3. Using a fixed-effect model where forest plots and I2 values suggest that heterogeneity is not an issue.

  4. Excluding cross-over studies.

Acknowledgements

The Cochrane Breast Cancer Group Review Group for editorial guidance and assistance.

The University of Western Sydney.

Appendices

Appendix 1. MEDLINE and EMBASE (via Embase.com)

1.     'breast tumour'

2.     'breast tumor'/exp OR 'breast tumor'

3.     'breast neoplasm'

4.     'breast cancer'/exp OR 'breast cancer'

5.     #1 OR #2 OR #3 OR #4

6.     'side effect*'/exp OR 'side effect*'

7.     'treatment-induced side effect*'

8.     treat* NEAR/5 'side effect'

9.     'distress syndrome'/exp OR 'distress syndrome'

10.   'psychological distress'/exp OR 'psychological distress'

11.   'adverse affect*'

12.   'side effect symptom*'

13.   'adverse effect symptom*'

14.   'toxic symptom*'

15.   'toxic effect symptom*'

16.   toxicit*

17.   'nausea'/exp OR nausea

18.   vomit*

19.   'hot flash'/exp OR 'hot flash*'

20.   'hot flushe*'

21.   'night sweat*'/exp OR 'night sweat*'

22.   'night sweat*'

23.   'night time awakening*'

24.   'sleep disturbance*'/exp OR 'sleep disturbance*'

25.   'sleep disturbances'

26.   depress*

27.   'psychological symptom*'

28.   'lymphedema' OR 'lymphedema'/exp OR lymphedema

29.   'lymphoedema' OR 'lymphoedema'/exp OR lymphoedema

30.   'post-mastectomy pain'

31.   'post mastectomy' NEAR/5 pain

32.   #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31

33.   'acupuncture'/exp OR 'acupuncture'

34.   'Chinese medicine'/exp OR 'Chinese medicine'

35.   'traditional Chinese medicine'/exp OR 'traditional Chinese medicine'

36.   TCM

37.   'acupuncture therapy'/exp OR 'acupuncture therapy'

38.   'scalp acupuncture'

39.   'auricular acupuncture'

40.   auricular NEAR/5 acupuncture

41.   'warming needle'

42.   'moxibustion'/exp OR moxibustion

43.   'electrical stimulation'/exp OR 'electrical stimulation'

44.   'electroacupuncture' OR 'electroacupuncture'/exp OR electroacupuncture

45.   #33 OR #34 OR #35 OR # 36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44

46.   randomised AND controlled AND trial

47.   controlled AND clinical AND trial

48.   randomi*ed:ab

49.   placebo:ab

50.   randomly:ab

51.   trial:ab

52.   groups:ab

53.   #46 OR #47 OR #48 OR 49 OR 50 OR 51 OR 52

54.   #5 AND #32 AND #45 AND 53

55.   #54 AND (humans)/lim

Appendix 2. WHO ICTRP

Basic search:

1.     breast cancer AND acupuncture

2.     breast cancer AND scalp acupuncture

3.     breast cancer AND auricular acupuncture

4.     breast cancer AND electroacupuncture

Advanced search:

1.     Title: acupuncture for treatment-related side effects in women with breast cancer

Recruitment status: ALL

2.     Condition: breast cancer

Intervention: acupuncture OR scalp acupuncture OR auricular acupuncture OR electroacupuncture OR acupuncture therapy

Recruitment status: ALL

3.     Condition: breast cancer

Intervention: (acupuncture OR scalp acupuncture OR auricular acupuncture OR electroacupuncture OR acupuncture therapy) NOT (acupressure OR laser acupuncture OR point injection)

Recruitment status: ALL

Appendix 3. ClinicalTrials.gov

Basic search:

1.     breast cancer AND acupuncture

2.     breast cancer AND scalp acupuncture

3.     breast cancer AND auricular acupuncture

4.     breast cancer AND electroacupuncture

Advanced search:

Title: acupuncture for treatment-related side effects in women with breast cancer

Recruitment: ALL studies

Study results: ALL studies

Study type: interventional studies 

1. Targeted search

Conditions: breast cancer

Interventions: acupuncture

Outcome measures : common toxicities

Sponsor/collaborators : unspecified

Sponsor (lead): unspecified

Study IDs: unspecified

Locations:

Stage 1: optional

Country 1: optional

Stage 1: optional

Country 1: optional

Stage 1: optional

Country 1: optional

Location terms: unspecified

Additional criteria:

Gender: studies with female participants

Age group: adult (18-65), senior (66+)

Phase: phase 1–4

Funded by: all others

Safety issue: un-tick 'Has an outcome measure designed as a safety issue'

First received: unspecified

Last updated: unspecified

Intervention: acupuncture OR scalp acupuncture OR auricular acupuncture OR electroacupuncture OR acupuncture therapy

Recruitment status: ALL

2. Targeted search

Conditions: breast cancer

Interventions: acupuncture

Outcome measures : nausea OR vomiting OR lyphoedema OR post-mastectomy pain

Sponsor/collaborators : unspecified

Sponsor (lead): unspecified

Study IDs: unspecified

Locations:

Stage 1: optional

Country 1: optional

Stage 1: optional

Country 1: optional

Stage 1: optional

Country 1: optional

Location terms: unspecified

Additional criteria:

Gender: studies with female participants

Age group: adult (18-65), senior (66+)

Phase: phase 1 – 4

Funded by: all others

Safety issue: un-tick 'Has an outcome measure designed as a safety issue'

First received: unspecified

Last updated: unspecified

Appendix 4. CNKI

1. Ai (carcinoma)

2. Dao Guan Nei Ai  (ductal carcinoma in situ)

3. Jin Run Xing Dao Guan Ai (invasive ductal cancer)

4. Ru Xian Ai (breast cancer)

5. Ru Ai (breast cancer)

6. Ru Xian E Xing Zhong Kuai (breast carcinoma)

7. Ru Xian E Xing Zhong Liu (breast carcinoma)

8. Ru Xian Jin Run Xing Dao Guan Ai (invasive ductal breast cancer)

9. Ru Xian Zhong Liu (breast tumour)

10. Ru Xian Zhong Liu Zhuan Yi (metastasis of breast cancer)

11. Ru Xian Zhong Kuai (breast lump)

12. 1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8 OR 9 OR 10 OR 11

13. Fu Zuo Yong (side effects)

14. Bu Liang Fan Ying (adverse effects)  

15. Kang Zhong Liu Yao/Fu Zuo Yong (oncology drugs/side effects)

16. Yao Wuo Bu Liang Fan Ying (drug adverse effects)

17. Du Fu Fan Ying (toxic and side effects)

18. Hua Liao (chemotherapy)

19. Fang Liao (radiotherapy)

20. Nei Feng Bi Zhi Liao (endocrine therapy)

21. Ru Ai Shuo He Teng Tong (post-mastectomy pain)

22. Shen Huo Zhi Liang (quality of life)

23. 13 OR 14 OR 15 OR 16 OR 17 OR 18 OR 19 OR 20 OR 21 OR 22 

24. Zhen Ci Liao Fa (acupuncture therapy)

25. Zhen Jiu (acupuncture and moxibustion)

26. Zhen Jiu Liao Fa (acupuncture and mosibustion therapy)

27. Zhen Jiu Lin Chuang (acupuncture and moxibustion clinical )

28. Zhen Jiu Zhi Liao (acupuncture and moxibustion treatment)

29. Dian Zhen (electro-acupuncture)

30. Dian Zhen Zhi Lao (electro-acupuncture treatment)

31. Er Zhen (auricular acupuncture)

32. Ti Zhen (body acupuncture)

33. Tou Zheng (scalp acupuncture)

34. 24 OR 25 OR 26 OR 27 OR 28 OR 29 OR 30 OR 31 OR 32 OR 33 

35. Lin Chuang (clinical)

36. Lin Chuang Yun Yong (clinical application)

37. Lin Chuang Zhi Liao (clinical treatment)

38. Lin Chuang Yan Jiu (clinical research)

39. Lin Chuang Guan Cha (clinical observation)

40. Lin Chuang Dui Zhao (clinical comparison)

41. Lin Chuang Liao Xiao (clinical therapeutic outcome)

42. 35 OR 36 or 37 OR 38 OR 39 OR 40 OR 41

43. 12 AND 23 AND 34 AND 42

Contributions of authors

XZ: conceptualised and wrote the protocol. She will search the English and Chinese databases, review trials and perform data extraction, data interpretation and assessment. She will jointly write the review.

AB: commented on and assisted with development of the protocol. He will contribute to data interpretation and will also jointly write the review.

EM: commented on and assisted with development of the protocol. He will specifically contribute to data interpretation and perform data assessment. He will also jointly write the review.

HC: commented on and assisted with development of the protocol. She will also jointly write the review.

WL: commented on and assisted with development of the protocol. He will also review trials and perform data extraction, data interpretation and assessment. He will jointly write the review.

Declarations of interest

None known.

Sources of support

Internal sources

  • The Cochrane Breast Cancer Group, Australia.

External sources

  • University of Western Sydney, Australia.

  • Tufts University, USA.

  • Dana-Farber Cancer Institute, USA.

  • Shanghai Longhua Hospital, China.

Ancillary