Surgery for Diagnosis and Treatment: Sentinel Lymph Node Biopsy in Breast Cancer.

Abstract

tumor, the sentinel node (SN), represented the status of the remaining nodes in the regional nodal drainage basin. His group first reported that histopathologic analysis of the SN detected by mapping the regional lymphatics with a vital blue dye accurately predicted the presence or absence of regional nodal metastases in patients with melanoma. 1 To determine if the concept could be generalized to include breast cancer, we modified Morton's technique used in melanoma and initiated a study in 1991 to investigate the feasibility of lymphatic mapping and sentinel lymph node dissection (SLND) in breast cancer patients. With no prior experience using this technique in breast cancer, a development period was required to define the technical aspects of the procedure. As it was soon discovered, the kinetics of blue dye migration in breast lymphatics were markedly different than in cutaneous lymphatics. Several factors affected the success of this technique, including patient selection, injection technique, dissection technique, and histopathologic evaluation of the SN. Next, we examined the ALND specimens of patients with histologically involved nodes to determine if the SN could have predicted the axillary status by chance alone. Thirty- four patients had a total of 751 lymph nodes removed, of which 63 (8%) were SNs and 688 (92%) were non-SNs. Tumor was detected in 39 (62%) SNs, while only 93 (14%) of 688 non-SNs were involved with tumor (P<0.0001). This suggested that breast cancer metastases occur through a nonrandom pathway that can be identified by SLND. It also suggested that random axillary biopsy or sampling could not recreate these results through chance alone. In the next report of this technique, we evaluated the first 162 patients undergoing successful SLND followed by completion ALND (SLND group) and compared them to 134 patients undergoing ALND alone (ALND group). 4 Although the groups were not randomized, they were contemporaneous and all procedures were performed at the same institutions by a single surgeon. The SN was evaluated by hematoxylin-eosin (H&E) staining and anticytokeratin IHC staining, while non-SNs were evaluated by H&E staining alone. Both groups had comparable clinical characteristics and a similar total number of axillary nodes excised. The SLND group had a 42% incidence of axillary metastases compared with 28% in the ALND group (P<0.05). This was primarily due to a dramatic increase in the detection of micrometastases by IHC in the SLND group. Sixteen percent of SLND patients had metastases less than 2 mm in size compared to 3% of the ALND group. Detection of micrometastases by both H&E staining (9% vs 3%) and IHC staining (7% vs 0%) increased with SLND. We concluded that SLND not only accurately predicts the status of the axillary nodes, but also improves axillary staging compared with standard ALND. This results from a focused histopathologic evaluation of the SN, which increases the detection of micrometastases using IHC staining of the SN. Unfortunately, the clinical significance of the IHC-detected nodal metastases is currently unknown, creating confusion in the clinical management of these patients who were upstaged by SLND. Since the technique of SLND was evolving, we reported a more recent series of 107 patients undergoing lymphatic mapping and SLND followed by ALND, using our mature technique. 5 We identified the SN in 94% of patients. There were no false-negative results, indicating a sensitivity and specificity of 100%. We attribute our increased success to refinements in technical details and indications for the procedure. Based on these results, a trial to investigate lymphatic mapping and SLND alone in patients with negative SN began in October 1995. This trial is soon to be reported and included T1 and T2 (less than or equal to 4 cm) tumors. To date no axillary recurrence has been seen in more than 300 cases at our institution.