Judy C. Boughey, MD, FACS
Professor of Surgery
As advances in systemic therapy improve our ability to individualize breast cancer treatment, and improve response rates and outcomes, it is important to reevaluate the most appropriate form of local-regional management. When chemotherapy is used in the neoadjuvant setting, response is determined surgically after the neoadjuvant chemotherapy. Response evaluation involves resection of any residual disease in the tumor bed in the breast, as well as staging of the ipsilateral axillary lymph nodes.
Increasingly, comprehensive imaging of the breast and the ipsilateral axilla is performed at initial presentation with breast cancer, including ipsilateral axillary ultrasound to evaluate the morphology of the axillary nodes sonographically. In cases where lymph nodes appear abnormal, percutaneous biopsy of ipsilateral nodes to evaluate for nodal involvement is performed at presentation. Thus, lower volume of nodal disease can be detected than when using physical examination alone. Surgical axillary staging after neoadjuvant chemotherapy is influenced by clinical nodal stage at presentation. In cases with clinically negative lymph nodes at presentation, staging of the regional lymph nodes with sentinel lymph node biopsy after neoadjuvant chemotherapy has been shown to have a similar false-negative rate to the use of sentinel lymph node surgery without any prior systemic therapy. Until recently, in cases documented to be node-positive at presentation, axillary lymph node dissection after completion of neoadjuvant chemotherapy was standard practice.
The ACOSOG Z1071 study was a prospective, single-arm phase II clinical trial designed to evaluate the false-negative rate of sentinel lymph node surgery in patients with biopsy-proven node-positive disease treated with neoadjuvant chemotherapy.
The primary endpoint of the study was the false-negative rate of sentinel lymph node surgery in patients with clinical N1 disease with two or more sentinel nodes resected. The study enrolled a total of 756 women across 136 institutions. The false-negative rate was 12.6%.1
The data also showed that when dual mapping agents were utilized, the false-negative rate was statistically lower at 10.8%. Additionally, when more than two sentinel nodes were resected, the false-negative rate fell to 9.1%. Other studies have also evaluated this question. The SN FNAC study conducted in Canada was a smaller study similar to Z1071 that showed a false-negative rate of 9.6% based on local site review of sentinel lymph node histology. When central review of the sentinel lymph nodes was utilized, the false-negative rate was 8.4%.2
Additionally, the SENTINA study conducted in Germany evaluated this question in patients who were clinically node-positive without requiring histological or cytological confirmation of nodal involvement at presentation. The researchers evaluated the role of sentinel lymph node biopsy in those patients who had normalization of the appearance of the lymph nodes on ultrasound examination.
This study reported a false-negative rate of 14.2% when all patients were evaluated; however, when limiting the evaluation to those patients with two or more sentinel nodes resected, the false-negative rate was 9.6%.3
Additionally, this study, similar to Z1071, showed that the false-negative rate decreased as the number of sentinel nodes resected increased.
As we reevaluate the appropriate axillary surgery for staging in patients with node-positive breast cancer, it becomes important to consider the likelihood of nodal response and the potential advantages of utilizing sentinel lymph node surgery.