Background: Axillary lymph node dissection has been an established surgical component of breast cancer management since the development of the radical mastectomy. However, the contribution of surgical local control to breast cancer survival has become controversial, and the procedure confers significant morbidity, including infection, seroma, and lymphedema. Sentinel lymph node dissection was developed for the accurate staging of tumor-draining axillary lymph nodes while minimizing the complications of axillary lymph node dissection. Current recommendations include sentinel lymph node dissection as part of disease staging, which provides adequate and sufficient surgical local control if the nodes are negative. When the sentinel nodes are positive for metastases, the patient proceeds to axillary lymph node dissection.

Cancer therapy has progressed significantly since axillary lymph node dissection was developed, and the decision to administer chemotherapy is dictated more by tumor-specific factors than by the presence of nodal metastases. To better characterize the role axillary lymph node dissection may play in breast cancer survival, the American College of Surgeons Oncology Group began the Z0011 trial in the late 1990s to evaluate survival in the current era of breast cancer management, which includes lumpectomy, adjuvant systemic therapy, and tangential-field radiation therapy.

The Study: This multicenter randomized controlled trial included women with histologically confirmed invasive breast carcinoma of 5 cm or less, with no palpable adenopathy and a positive sentinel lymph node, who were treated with lumpectomy to negative margins. Women who had three or more positive sentinel lymph nodes, matted nodes, gross extranodal disease, or previously received neoadjuvant hormonal therapy or chemotherapy were excluded. Women were stratified by age (50 years or younger, and older than 50 years), tumor size (1 cm or less, more than 1 cm to 2 cm, and more than 2 cm), and estrogen-receptor status. Women were randomized to axillary lymph node dissection of at least 10 nodes or no further axillary-specific intervention. Follow-up history and physical examinations were performed semiannually for the first three years and then annually. All participants required annual mammography.

The primary end points were overall survival from the time of randomization until death from any cause, and the incidence of surgical morbidities. A secondary end point was disease-free survival. Assuming survival was 80 percent at five years in optimally treated women with positive nodes, the authors defined clinical noninferiority as survival in the sentinel lymph node dissection–alone group of at least 75 percent of that in the axillary lymph node dissection group. The initial study design called for 1,900 participants with four interim analyses and one final analysis after five years to determine overall survival. However, the study was closed early because of a much lower than expected mortality rate in pooled data. It was determined that it would have taken 20 years of follow-up to accrue the expected 500 deaths.

Results: Of the 891 patients enrolled, 445 were assigned to the axillary lymph node dissection group, and 446 to the sentinel lymph node dissection–alone group. There were no significant differences in patient age, disease characteristics, percentage and types of chemotherapy, hormonal therapy administered, and rates of whole-breast radiation therapy between the two treatment groups. Median follow-up was 6.3 years, at which point there were 42 deaths in the sentinel lymph node dissection–alone group and 52 deaths in the axillary lymph node dissection group, which was statistically significant for noninferiority (P = .008). The five-year survival rates were 92.5 percent for the sentinel lymph node dissection–alone group and 91.8 percent for the axillary lymph node dissection group, and outcomes did not change when accounting for the status of estrogen and progesterone receptors. Disease-free survival rates were similar between the groups, with five-year local recurrence rates of 1.6 percent in the sentinel lymph node dissection–alone group and 3.1 percent in the axillary lymph node dissection group.

Conclusion: In women treated with lumpectomy and systemic therapy for breast cancer, sentinel lymph node dissection alone does not negatively affect survival compared with extensive axillary lymph node dissection.