Sentinel lymph node biopsy in breast cancer : procedural issuses and prognostic impact of detecting micrometastases

The introduction of the sentinel lymph node biopsy (SLNB) in breast cancer patients raised several procedure-related clinical questions as well as questions regarding the implications of the obtained staging information. As a minimally invasive operative procedure as well as an enhanced pathological staging procedure SLNB has become standard of care in breast cancer patients. Part of the SLNB is the injection of a radiofarmacon during lymphoscintigraphy. Different injection techniques translate into different drainage patterns. Ultrasound (US) guided radiofarmacon injection provides a uniform procedure for both palpable and nonpalpable tumors with similar results for lymphoscintigraphic visualization and surgical retrieval rate of axillary and internal mammary sentinel lymph nodes (SLNs). When SLNs contain metastase(s), a supplementary axillary lymph node dissection (ALND) is advised. Intraoperative frozen section (FS) analysis of SLNs enables a prompt ALND during the first operation, sparing the patient a second operation. The yield of FS is limited, and discordant FS results (i.e. the absence of SLN metastases in the FS and the presence of metastases following the definitive pathology examination of SLNs) still necessitates a complementary ALND. While discordant FS results were in itself relatively common, the complementary ALND rarely results in postsurgical treatment adjustments. ALND is performed to obtain locoregional control as well as for staging purposesbut comes with significant morbidity. To reduce this ALND-related morbidity, there is a recent interest in the different lymphatic drainage patterns of the breast and arm within the axilla. The different lymphatic patterns may be visualized by doing “ARM”: axillary reverse mapping. ARM is a way of reducing morbidity by selectively removing lymph nodes from the axilla and sparing axillary nodes and lymphatic’s that drain the arm. In a feasibility study we observed the absence of metastases in the ARM lymph nodes in patients who had metastases in their SLNs, while the frequency of ARM-node involvement was 22% in patients who had axillary metastases proven by preoperative US guided cytology. The sensitivity of the SLNB procedure to detect axillary metastases is not 100%. False negative rates are reported in approximately 3% of the patients, implying that the latter proportion of patients will have metastases in the axilla despite a “clean” SLN. Expectedly, patients with a false-negative SLN may develop overt lymph node metastases during follow-up but the extent of the clinical problem is unknown. In a multi-institutional cohort analyses we learned that axillary relapse rates in N0 patients are low. The annual relapse rate was approximately 0.2%. In addition, axillary relapses were significantly more common in patients who underwent ablative surgery, most likely due to the radiotherapy in patients undergoing breast conserving therapy. There is a lively debate regarding the relevance of minimal SLN involvement. In a single and multi-institutional cohort, in terms of overall and disease free survival, we observed no significant differences between N0 and N1mi, while survival in N1 patients was significantly worse. Based on these results we conclude that the presence of lymph node micrometastases should in itself not be a reason to advocate adjuvant systemic treatmen