CRD summary

The review concluded that sentinel lymph node biopsy in early breast cancer resulted in a significant reduction in postoperative morbidity, improved quality of life and comparable regional control without reducing overall survival and disease-free survival. Substantial differences between the included studies and the small number of trials in the pooled analyses for postoperative morbidity suggest some caution when interpreting these results.

Authors' objectives

To compare the effectiveness and safety of sentinel lymph node biopsy with axillary lymph node dissection in early breast cancer.

Searching

PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to March 2011 with no language restrictions. Search terms were reported. Reference lists were checked and experts in the area were contacted for any additional relevant studies.

Study selection

Randomised controlled trials (RCTs) that compared sentinel lymph node biopsy with axillary lymph node dissection in adult (18 years and older) women with histologically confirmed primary invasive breast carcinoma. Primary outcomes included overall survival, disease-free survival and regional lymph node recurrence (ipsilateral axilla). Secondary outcomes included postoperative morbidity and quality of life. The following were excluded: patients who were pregnant, had a multicentric tumour or had previous ipsilateral breast or axillary surgery (other than benign biopsy).

Of the eight included trials, only one trial included patients with a positive sentinel lymph node. The process of sentinel lymph node identification varied across trials. Where reported, the most common type of surgery undertaken was breast conservation treatment followed by mastectomy. Adjuvant therapy included hormonal replacement therapy, radiotherapy to the breast and chemotherapy. Histologic type was categorised into ductal, lobular and other. Most participants had a tumour size of 20mm or less. Tumour grades ranged from I to III.

Two reviewers independently selected trials for inclusion in the review. Any disagreement was resolved through discussion.

Assessment of study quality

The quality of the included trials was assessed using the Cochrane Risk of Bias Tool for adequate sequence generation, allocation concealment, blinding, incomplete outcome data addressed, free of selective reporting and free of other biases. Each criteria was rating as being of low risk, unclear risk or high risk.

The authors did not state how many reviewers were involved in the assessment of trial quality.

Data extraction

Two reviewers independently extracted hazard ratios (HRs) and their 95% confidence intervals (CIs) for the outcomes of overall survival and disease-free survival. Data were also extracted to enable calculation of odds ratios (ORs) for the outcomes of lymph node recurrence and postoperative morbidity. Where additional information was required the authors of the original trials were contacted. Final agreement was achieved through discussion.

Methods of synthesis

Pooled hazard ratios and odds ratios with 95% CIs were calculated using a fixed-effect model, unless significant statistical heterogeneity was found and a random-effects model was used. Heterogeneity was assessed using Χ².

Subgroup analyses (positive sentinel lymph node versus negative sentinel lymph node) and sensitivity analyses (exclusion of individual trials from the analysis) were performed. Publication bias was assessed with examination of a funnel plot as well as with Begg's and Egger tests.

Where pooling of trials was not possible a narrative synthesis was presented.

Results of the review

Eight RCTs were included in the review (8,560 participants, range 225 to 3,986). All trials reported adequate sequence generation and allocation concealment and dealt with incomplete outcome data. It was unclear whether trials were blinded or free of selective reporting. Overall the methodological quality of the included trials was considered to be good.

No statistically significant between-group differences were found for overall survival, disease-free survival and regional lymph node recurrence (ipsilateral axilla). There was no evidence of significant statistical heterogeneity. Subgroup analyses did not significantly alter the main findings.

A significantly lower rate of lymphedema six months after surgery (OR 0.24, 95% CI 0.11 to 0.53; five RCTs), numbness or paraesthesia six months after surgery (OR 0.19, 95% CI 0.11 to 0.33; six RCTs), wound infection within the first 30 days (OR 0.50, 95% CI 0.36 to 0.70; two RCTs) and axillary seroma formation within the first 30 days (OR 0.39, 95% CI 0.31 to 0.49; three RCTs) was found in the sentinel lymph node biopsy group compared with the axillary lymph node dissection group. Significant statistical heterogeneity was found for lymphedema (Ι²=85.6%) and paraesthesia (Ι²=92.7%) analyses.

Meta-analysis was not conducted for arm mobility due to mixed data but all included studies found that there was a significantly greater impairment of arm movement (especially arm flexion and abduction) in the axillary lymph node dissection group compared to sentinel lymph node biopsy.

Four of five trials reported that quality of life was better in the sentinel lymph node biopsy group than the axillary lymph node dissection group.

No evidence of publication bias was found. Accuracy results were presented in the paper.

Authors' conclusions

Compared with axillary lymph node dissection, sentinel lymph node biopsy in early breast cancer resulted in a significant reduction in postoperative morbidity, improved quality of life and comparable regional control without reducing overall survival and disease-free survival. Sentinel lymph node biopsy can be recommended as preferred care for negative sentinel lymph node patients and selected patients with sentinel lymph node micrometastasis.

CRD commentary

The review question was supported with defined inclusion and exclusion criteria. Three databases were searched, unrestricted by language and included one with details from unpublished sources. Appropriate steps were taken to minimise the likelihood of error and bias in the selection of trials and extraction of data. It was not clear whether similar steps were taken for the validity assessment. Trial quality was assessed using appropriate criteria and individual results were presented.

Standard methods were used to pool trials. Heterogeneity was explored. Limitations in the review acknowledged by the authors included use of different inclusion criteria and variation in terms of surgeon skill, scale of surgery and types of adjuvant therapy.

In general this was a well-conducted review of good quality trials but substantial heterogeneity and the small number of trials in the pooled analyses of the secondary outcomes suggest that some caution should be taken when interpreting these results.

Implications of the review for practice and research

Practice: The authors stated that while axillary lymph node dissection remained the standard management in breast cancer patients with sentinel lymph node micrometastasis, sentinel lymph node biopsy can be recommended as preferred care for negative sentinel lymph node patients and selected patients with sentinel lymph node micrometastasis. However, treatment should always be tailored to a patients preference taking into account risk-benefits such as physical activity and prognosis.

Research: The authors stated that further research was required to establish whether sentinel lymph node biopsy was possible in sentinel lymph node positive patients.

Funding

Not reported.

Bibliographic details

Wang Z, Wu LC, Chen JQ. Sentinel lymph node biopsy compared with axillary lymph node dissection in early breast cancer: a meta-analysis. Breast Cancer Research and Treatment 2011; 129(3): 675-689. [PubMed: 21743996]

Original Paper URL

http://www.springerlink.com/content/c614882543446671/

Indexing Status

Subject indexing assigned by NLM

MeSH

Axilla /pathology /surgery; Breast Neoplasms /mortality /pathology /surgery; Disease-Free Survival; Female; Humans; Lymph Node Excision /methods; Lymphatic Metastasis /diagnosis; Middle Aged; Randomized Controlled Trials as Topic; Sentinel Lymph Node Biopsy /methods

AccessionNumber

12011006283

Database entry date

05/10/2012

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.