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

Abstract

Summary Background Sentinel node surgery was designed to minimize side effects of lymph node surgery but still offer outcomes equivalent to axillary dissection. The aims of NSABP Protocol B-32 were to determine whether sentinel node resection in breast cancer patients achieves the same survival and regional control as axillary dissection but with fewer side effects. Methods 5611 women with invasive breast cancer were randomly assigned to sentinel node resection plus axillary dissection (Group 1) or to sentinel node resection alone with axillary dissection only if sentinel nodes were positive (Group 2). Random assignment was done at the NSABP Biostatistical Center and accomplished via using a biased coin minimization approach. Stratification variables were age at entry (≤ 49,≥ 50), clinical tumor size (≤ 2.0 cm, 2.1 – 4 cm, ≥ 4.1 cm), and surgical plan (lumpectomy, mastectomy). Sentinel node resection was done using blue dye and radioactive tracer. As pre-specified in the protocol, analyses of endpoint data were performed according to the randomized group assignments on patients who were assessed at the time of randomization as having pathologically negative sentinel nodes (3989 patients). The endpoint analyses were performed on all such patients who had follow-up information regardless of their eligibility status (3986 patients). The primary endpoint for the study was overall survival. All deaths regardless of cause were included. The mean time on study for the 3986 sentinel node-negative patients with follow-up information was 95.6 months (range: 70.1 – 126.7 months). Findings A total of 309 deaths were reported in the 3986 sentinel node-negative patients with follow-up information. Log-rank comparison of overall survival in Groups 1 and 2 yielded an unadjusted hazard ratio of 1.20 (95% confidence interval [CI]; 0.96 –1.50, P = 0.12). Eight-year Kaplan-Meier estimates for overall survival are 91.8% in Group 1 and 90.3% in Group 2. Treatment comparisons for disease-free survival yielded an unadjusted hazard ratio of 1.05 (95% CI: 0.90 – 1.22, P=0.54). Eight-year Kaplan-Meier estimates for disease-free survival are 82.4% in Group 1 and 81.5% in Group 2. There were 8 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 evaluation of survival and regional control. Interpretation Overall survival, disease-free survival, and regional control were statistically equivalent between groups. When the sentinel node is negative, sentinel node surgery alone with no further axillary dissection is an appropriate, safe, and effective therapy for breast cancer patients with clinically negative lymph nodes.