Sentinel Lymph Node Dissection With and Without Axillary Dissection in Women With Invasive Breast Cancer and Sentinel Node Metastasis: A Randomized Clinical Trial

[ ABSTRACT ]

Context Sentinel lymph node dissection (SLND) accurately identifies nodal metastasis of early breast cancer. Objective To determine the impact of complete axillary lymph node dissection (ALND) on survival of patients with sentinel lymph node (SLN) metastasis of breast cancer. Design and Setting The 115 sites participating in the American College of Surgeons Oncology Group Z0011 trial enrolled patients from May 1999 to December 2004. In this phase III noninferiority trial, patients with SLN metastasis were randomized to ALND or no further axillary treatment. Targeted enrollment was 1900 women, with final analysis after 500 deaths, but the trial closed early because mortality rate was lower than expected. Patients Women with clinical T1–T2 invasive breast cancer, no palpable adenopathy, and 1–2 SLNs containing metastases identified by frozen section, touch preparation, or hematoxylin and eosin staining on permanent section. Interventions All patients underwent lumpectomy and tangential whole-breast irradiation. Those randomized to ALND underwent dissection of ≥10 nodes. Systemic therapy was at the discretion of the treating physician. Main Outcome Measures Overall survival (OS) was the primary endpoint, with a noninferiority margin of a one-sided hazard ratio of 1.3 or less favoring ALND. Disease-free survival (DFS) was a secondary endpoint. Results Clinical and tumor characteristics were similar between 445 patients randomized to ALND and 446 randomized to SLND alone. However, the median number of nodes removed was 17 with ALND and 2 with SLND alone. At a median follow-up of 6.3 years (last follow-up date 03/04/2010), 5-year OS was 91.8% (95% CI: 89.1 to 94.5) with ALND and 92.5% (95% CI: 90.0 to 95.1) with SLND alone; 5-year DFS was 82.2% (95% CI: 78.3 to 86.3) with ALND and 83.9% (95% CI: 80.2 to 87.9) with SLND alone. Hazard ratio for treatment-related OS was 0.79 (90% CI: 0.56 to 1.11) without adjustment and 0.87 (90% CI: 0.62 to 1.23) after adjusting for age and adjuvant therapy. Conclusions Among patients with limited SLN metastatic breast cancer treated with breast conservation and systemic therapy, the use of SLND compared with ALND did not result in inferior survival.