Sentinel lymph node as a new marker for therapeutic planning in breast cancer patients

BACKGROUND AND OBJECTIVES: Literature review suggests that the sentinel lymph node (sN) represents a reliable predictor of axillary lymph node status in breast cancer patients; however, some important issues, such as the optimisation of the technique for the intraoperative identification of the sN, the role of intraoperative frozen section examination of the sN, and the clinical implications of sN metastasis as regards the surgical management of the axilla, still require further confirmation. The authors aimed (1) to assess the feasibility of sN identification with a combined approach (vital blue dye lymphatic mapping and radioguided surgery, RGS) and the specific contribution of either techniques to the detection of the sN, (2) to determine the accuracy and usefulness of intraoperative frozen section examination of the sN in order to perform a one-stage surgical procedure, and (3) to define how the sN might modulate the therapeutic planning in different stages of disease. MATERIALS AND METHODS: From October 1997 to June 2001, 334 patients with early-stage (T(1-2) N(0) M(0)) invasive mammary carcinoma underwent sN biopsy; the average age of patients was 61.5 years (range, 39-75 years). In a subset of 153 patients, both vital blue dye (Patent Blue-V) lymphatic mapping and RGS were used to identify the sN, and the relative contribution of each of the two techniques was assessed. RESULTS: In the whole group, the sN was identified in 326 of 334 patients (97.6%), and 105 of 326 patients (37.3%) had positive axillary lymph nodes (pN+). In 9 of 105 pN+ patients, the definitive histologic examination of the sN did not show metastases but these were detected in non-sN, thus giving an 8.6% false-negative rate, a negative predictive value of 94.5% (156/165), and an accuracy of 96.5% (252/261). As regards the specific contribution of the two different techniques used in the identification of the sN, the detection rate was 73.8% (113/153) with Patent Blue-V alone, 94.1% (144/153) with RGS alone, and 98.7% (151/153) with Patent Blue-V combined with RGS (P < 0.001). Noteworthy, whenever the sN was identified, the prediction of axillary lymph node status was remarkably similar (93-95% sensitivity; 100% specificity; 95-97% negative predictive value, and 97-98% accuracy) whichever of the three procedures was adopted (Patent Blue-V alone, RGS alone, or combined Patent Blue-V and RGS). Intraoperative frozen section examination was performed in 261 patients, who had at least one sN identified, out of 267 patients who underwent complete axillary dissection; 170 patients had histologically negative sN (i.o. sN-) and 91 patients histologically positive sN (i.o. sN+). All 91 i.o. sN+ were confirmed by definitive histology, whereas in 14 of 170 i.o. sN- patients (8.2%) metastases were detected at definitive histology. As regards the correlation between the size of sN metastasis, the primary tumour size, and the status of non-sN in the axilla, micrometastases were detected at final histology in 23 patients and macrometastases in 82 patients. When only micrometastases were detected, the sN was the exclusive site of nodal metastasis in 20 of 23 patients (86.9%) while in 3 patients with tumour size larger than 10 mm micrometastases were detected also in non-sN. Macrometastases were never detected in pT(1a) breast cancer patients; the sN was the exclusive site of these metastases in 30 patients (36.6%), while in 52 patients (63.4%) there were metastases both in sN and non-sN. CONCLUSIONS: Sentinel lymphadenectomy can better be accomplished when both procedures (lymphatic mapping with vital blue dye and RGS) are used, because of the significantly higher sN detection rate, although the prediction of axillary lymph node status remains remarkably similar whichever method is used. The intraoperative frozen section examination proved to be rather accurate in predicting the actual pathologic status of the sN, with a negative predictive value of 91.8%; in 35% of patients it allowed sN biopsy and axillary dissection to be performed in a one-stage surgical procedure. Finally, specific clinical and histopathologic features of the primary tumour and sN might be used to tailor the loco-regional and systemic treatment in different clinical settings, such as in ductal carcinoma in-situ (DCIS), early-stage invasive breast cancer, and patients with large breast cancer undergoing neo-adjuvant CT for breast-saving surgery as well as elderly patients with operable breast cancer.