Axillary Dissection vs No Axillary Dissection in Women With Invasive Breast Cancer and Sentinel Node Metastasis (ACOSOG Z11 Trial)

A Randomized Clinical Trial

Sentinel lymph node dissection (SLND) accurately identifies nodal metastasis of early breast cancer, but it is not clear whether further nodal dissection affects survival. Objective To determine the effects of complete axillary lymph node dissection (ALND) on survival of patients with sentinel lymph node (SLN) metastasis of breast cancer.

The American College of Surgeons Oncology Group Z0011 trial, a phase 3 noninferiority trial conducted at 115 sites and enrolling patients from May 1999 to December 2004. Patients were women with clinical T1-T2 invasive breast cancer, no palpable adenopathy, and 1 to 2 SLNs containing metastases identified by frozen section, touch preparation, or hematoxylin-eosin staining on permanent section. Targeted enrollment was 1900 women with final analysis after 500 deaths, but the trial closed early because mortality rate was lower than expected.

Interventions All patients underwent lumpectomy and tangential whole-breast irradiation. Those with SLN metastases identified by SLND were randomized to undergo ALND or no further axillary treatment. Those randomized to ALND underwent dissection of 10 or more nodes. Systemic therapy was at the discretion of the treating physician.

Main Outcome Measures Overall survival was the primary end point, with a noninferiority margin of a 1-sided hazard ratio of less than 1.3 indicating that SLND alone is noninferior to ALND. Disease-free survival was a secondary end point.

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, 5-year overall survival was 91.8% with ALND and 92.5%  with SLND alone; 5-year disease-free survival was 82.2% with ALND and 83.9%  with SLND alone. The hazard ratio for treatment-related overall survival was 0.79 without adjustment and 0.87 after adjusting for age and adjuvant therapy.

Conclusion Among patients with limited SLN metastatic breast cancer treated with breast conservation and systemic therapy, the use of SLND alone compared with ALND did not result in inferior survival.



Surgical Morbidities

Paresthesias, shoulder pain, weakness, lymphedema, and axillary web syndrome are recognized morbidities of ALND. As previously reported,the rate of wound infections, axillary seromas, and paresthesias among patients in the Z0011 trial was higher for the ALND group than for the SLND-alone group (70% vs 25%, P < .001).

 Lymphedema in the ALND group was significantly more common by subjective report and also tended to be higher by objective assessment of arm circumference. These findings are in accordance with other randomized comparisons of SLND with vs without ALND.

Adverse surgical effects were reported in 70% (278 of 399) of patients after SLND + ALND and 25% (103 of 411) after SLND alone (P≤ .001). Patients in the SLND + ALND group had more wound infections (P≤ .0016), seromas (P≤ .0001), and paresthesias (P≤ .0001) than those in the SLND-alone group.

At 1 year, lymphedema was reported subjectively by 13% (37 of 288) of patients after SLND + ALND and 2% (six of 268) after SLND alone (P≤ .0001). The difference between the two groups' lymphedema, assessed by arm measurements at 30 days (P = .36), 6 months (P = .22), and 1 year (P = .078), although close to the cutoff for significance at 1 year, was not significant. BPIs occurred in less than 1% of patients.