Sentinel lymph node dissection only versus complete axillary lymph node dissection in early invasive breast cancer: A systematic review and meta-analysis

Abstract

Background

The Z0011-study, a landmark randomised controlled trial (RCT) challenged the benefits of complete axillary lymph node dissection (ALND) compared with sentinel lymph node dissection only (SLND) in breast cancer patients with positive sentinel nodes. The study, however, has been criticised for lack of power and low applicability. The aim of this review was to systematically assess the evidence on the comparative benefits and harms of ALND versus SLND for sentinel node positive breast cancer patients.

Methods

We systematically searched PubMed, Embase, the Cochrane Library, and reference lists of pertinent review articles from January 2006 to August 2011. We dually reviewed the literature and rated the risk of bias of each study. For effectiveness, we included RCTs and observational studies of at least 1 year follow-up. In addition, we considered studies conducted in sentinel node-negative women to assess the risk of harms. If data were sufficient, we conducted random effects meta-analysis of outcomes of interest.

Results

Meta-analysis of three studies with 50,120 patients indicated similar 5-year survival and regional recurrence rates between patients treated with ALND or SLND, although prognostic tumour characteristics varied among the 3 study-populations. Results from 6 studies on more than 11,500 patients reported a higher risk for harms for ALND than SLND. Long-term evidence on pertinent health outcomes is missing.

Conclusion

The available evidence indicates that for some women with early invasive breast cancer SLND appears to be a justifiable alternative to ALND. Surgeons need to discuss advantages and disadvantages of both approaches with their patients.

Introduction

Breast cancer is the most common malignancy in women, comprising 16% of all female cancers.¹ In 2008, approximately 332,800 cases of breast cancer occurred in the European Union and almost 90,000 women died of the disease.² Ecologic studies in Europe have demonstrated a rise in the incidence of breast cancer over the past decades, probably attributable to an increase in breast cancer screening.3, 4 Despite the increase in the number of breast cancer sufferers, mortality from the disease has substantially decreased. This has been attributed to both breast cancer screening programmes (which enable detection of cancers at an earlier stage) and improved therapeutic possibilities.⁵

Axillary surgery is a crucial part of the treatment regimen for early invasive breast cancer. The surgical approach is determined by the staging and the involvement of axillary nodes.6, 7 In patients with positive axillary nodes, breast cancer-specific mortality rises markedly.⁸ Most guidelines recommend sentinel lymph node dissection (SLND) for the staging of the disease in women with clinically negative lymph nodes.6, 7 In SLND the surgeon injects dye, traces and selectively resects lymph nodes draining the primary tumour. When SLND is performed according to a standardised and quality-assured technique, accurate staging of the number of positive lymph nodes or the ratio of involved to examined lymph nodes can be used to determine further treatment strategies.6, 7, 9, 10, 11, 12, 13

In women with early invasive breast cancer without metastases in sentinel lymph nodes no further dissection of nodes in the local lymph drainage region is recommended. Most clinical practice guidelines suggest complete axillary lymph node dissection (ALND) in women with early invasive breast cancer and micro- or macro-metastatic disease.13, 15 The National Institute for Health and Clinical Excellence differentiates micrometastasis and isolated tumour cells and regards patients found to have isolated tumour cells as lymph node negative with no recommendation for any further axillary surgery.

A recent randomised controlled trial (RCT) conducted by the American College of Surgeons Oncology Group (ASOG Z0011 study) challenges the utility of ALND in women with early invasive breast cancer and positive sentinel nodes.16, 17, 18 Results indicated that ALND does not lead to a survival benefit compared with SLND only. The ASOG concluded that in patients with clinically-negative axillary lymph nodes, the use of ALND is not justified.16, 17, 18 This finding has been controversial, particularly because the Z0011 study failed to enrol the estimated sample size to meet the primary objective.19, 20, 21, 22, 23 Some authors argue that the waning utility of ALND has to be recognised and treatment guidelines need to be changed accordingly.21, 22, 23 Others claim that the Z0011 study results are not applicable to larger populations because it enrolled a greater proportion of oestrogen-receptor positive tumours compared with the current US-population and details about the initiation and intensity of adjuvant chemotherapy are not provided.19, 20

To date, no systematic review has assessed the comparative benefits and harms of SLND and ALND in women with T1 or T2 breast cancer and positive sentinel nodes. Our objective was to review systematically the available evidence from RCTs and observational studies to determine the comparative benefits and risks of these two surgical approaches.