Elsevier

The Lancet Oncology

Volume 11, Issue 10, October 2010, Pages 927-933
The Lancet Oncology

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Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial

https://doi.org/10.1016/S1470-2045(10)70207-2Get rights and content

Summary

Background

Sentinel-lymph-node (SLN) surgery was designed to minimise the side-effects of lymph-node surgery but still offer outcomes equivalent to axillary-lymph-node dissection (ALND). The aims of National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-32 were to establish whether SLN resection in patients with breast cancer achieves the same survival and regional control as ALND, but with fewer side-effects.

Methods

NSABP B-32 was a randomised controlled phase 3 trial done at 80 centres in Canada and the USA between May 1, 1999, and Feb 29, 2004. Women with invasive breast cancer were randomly assigned to either SLN resection plus ALND (group 1) or to SLN resection alone with ALND only if the SLNs were positive (group 2). Random assignment was done at the NSABP Biostatistical Center (Pittsburgh, PA, USA) with a biased coin minimisation approach in an allocation ratio of 1:1. Stratification variables were age at entry (≤49 years, ≥50 years), clinical tumour size (≤2·0 cm, 2·1–4·0 cm, ≥4·1 cm), and surgical plan (lumpectomy, mastectomy). SLN resection was done with a blue dye and radioactive tracer. Outcome analyses were done in patients who were assessed as having pathologically negative sentinel nodes and for whom follow-up data were available. The primary endpoint was overall survival. Analyses were done on an intention-to-treat basis. All deaths, irrespective of cause, were included. The mean time on study for the SLN-negative patients with follow-up information was 95·6 months (range 70·1–126·7). This study is registered with ClinicalTrials.gov, number NCT00003830.

Findings

5611 women were randomly assigned to the treatment groups, 3989 had pathologically negative SLN. 309 deaths were reported in the 3986 SLN-negative patients with follow-up information: 140 of 1975 patients in group 1 and 169 of 2011 in group 2. Log-rank comparison of overall survival in groups 1 and 2 yielded an unadjusted hazard ratio (HR) of 1·20 (95% CI 0·96–1·50; p=0·12). 8-year Kaplan-Meier estimates for overall survival were 91·8% (95% CI 90·4–93·3) in group 1 and 90·3% (88·8–91·8) in group 2. Treatment comparisons for disease-free survival yielded an unadjusted HR of 1·05 (95% CI 0·90–1·22; p=0·54). 8-year Kaplan-Meier estimates for disease-free survival were 82·4% (80·5–84·4) in group 1 and 81·5% (79·6–83·4) in group 2. There were eight regional-node recurrences as first events in group 1 and 14 in group 2 (p=0·22). Patients are continuing follow-up for longer-term assessment of survival and regional control. The most common adverse events were allergic reactions, mostly related to the administration of the blue dye.

Interpretation

Overall survival, disease-free survival, and regional control were statistically equivalent between groups. When the SLN is negative, SLN surgery alone with no further ALND is an appropriate, safe, and effective therapy for breast cancer patients with clinically negative lymph nodes.

Funding

US Public Health Service, National Cancer Institute, and Department of Health and Human Services.

Introduction

Axillary-lymph-node dissection (ALND) for breast cancer is a procedure designed to maximise survival and regional control and to establish nodal classification. However, this procedure is associated with short-term and long-term side-effects in a substantial number of patients.1, 2 Sentinel-lymph-node (SLN) resection was designed to minimise the side-effects of lymph-node surgery, but still offer outcomes equivalent to ALND.

The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial was therefore designed to establish whether SLN resection achieves the same therapeutic outcomes as ALND, but with fewer side-effects. Primary endpoints of the B-32 trial were survival, regional control, and morbidity. Technical outcomes and assessment of the training methods for this trial have been reported previously.3, 4 Patient-reported outcomes and morbidity related to range of motion, oedema, pain, and sensory defects have also been reported.5, 6 An ancillary pathology study assessing survival according to the detection of occult node metastases in 3887 SLN-negative patients has also been completed and will be reported separately.

We report the primary outcome survival data from the NSABP B-32 trial, which aimed to establish whether SLN resection in patients with SLN-negative breast cancer achieves the same survival and regional control as ALND, but with fewer side-effects. The data presented are based on a randomised controlled trial that used standardised surgical and pathological methods to ensure that the primary outcomes were as comparable as possible between treatment groups.

Section snippets

Patients

Between May 1, 1999, and Feb 29, 2004, a randomised controlled phase 3 trial was done at 80 institutions in Canada and the USA. Women with invasive breast cancer and clinically negative nodes were randomly assigned to SLN resection plus ALND (group 1) or to SLN resection alone with ALND only if SLNs were positive (group 2). Patients in both groups with pathologically negative SLNs were monitored at 4–6 month intervals for overall survival, disease-free survival, and regional control. Monitoring

Results

Figure 1 shows the trial profile. Women with clinically negative axillary lymph nodes, as assessed by physical examination, were randomly assigned to group 1 or group 2. 3989 patients (71·1%) of 5611 were SLN-negative, of whom 3986 (99·9%) had follow-up data. Random assignment of patients to the two treatment groups was balanced according to age, clinical tumour size, and surgical treatment plan (table 1).

The use of systemic adjuvant therapy was well balanced, with 85·1% (1680 of 1975 patients)

Discussion

Our trial shows that overall survival, disease-free survival, and regional control were all statistically equivalent in SLN-negative patients who had an ALND (group 1) or SLN surgery alone (group 2). The survival difference between the groups was less than 2% and any variation under that threshold is not significant. In a trial of this size we did not expect exact numerical duplication of events. In group 1, 75 patients had at least one positive non-sentinel node and 95% of this subset (71

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