Low volume metastases in breast cancer sentinel nodes: A diagnostic and therapeutic challenge

Abstract

A SN biopsy is an accurate method to assess nodal status in breast cancer patients and has largely replaced the traditional axillary lymph node dissection (ALND) as an initial staging procedure. The clinical scenarios for the use of a SN biopsy are expanding. We reviewed the literature regarding the role of a SN biopsy in patients with ductal carcinoma in situ (DCIS) and following neoadjuvant chemotherapy. We concluded that it could be considered on an individual basis, but we think there is insufficient evidence to recommend this as a standard procedure in these patients. Selective targeting of the SN with extensive pathological assessment increased the detection rate of small metastases with unknown clinical significance. This phenomenon is reflected by the International Union Against Cancer (UICC) system and by the 6th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, which defined metastases in three categories based on size: isolated tumor cells (ITC) (?0.2 mm), micrometastases (> 0.2- ? 2 mm) and macrometastases (> 2 mm). Although patients with ITC are staged as N0, there is no generally accepted approach regarding local control in this group. The published literature reported an overall pooled risk of higher echelon lymph node involvement (further denoted as non-SNs) of 12.3% after finding ITC in the SN. Because the majority of patients with SN ITC had non-SN macrometastases, there might be an indication for an ALND for those patients with SN ITC without other indications for adjuvant systemic therapy. A substantial proportion of patients with SN involvement do not have non-SN involvement. We assessed the predictive value of the SN tumor load (defined as the area% of the SN involved by tumor) and its micro-anatomic location, for non-SN involvement. Based on these features however, we could not select a subgroup of patients without non-SN involvement. Previous studies suggested that small epithelial deposits in lymph nodes may represent mechanically displaced benign or malignant epithelial cells, rather than true metastases. We therefore assessed the malignant potential of ITC by nuclear morphometry and immunohistochemistry. The results of these analyses suggest that some of these deposits represent benign or degenerated malignant epithelium lacking outgrowth potential. Since the distinction between ITC, micro-and macrometastases directly affects therapeutic decisions making, it is important to have a reproducible pathological staging method that provides a prognostic separation. We compared some refinements of the current definitions and offer suggestions regarding its use in lobular breast carcinoma patients. The unknown prognostic relevance of micrometastases and ITC leads to different opinions regarding adjuvant therapy. We evaluated the prognostic relevance of these metastases and the impact of adjuvant systemic therapy in a large nationwide Dutch cohort study and demonstrated a negative prognostic impact of both ITC and micrometastases in early stage breast cancer patients not receiving adjuvant systemic therapy. Furthermore, disease recurrence was reduced in patients treated with adjuvant systemic therapy. Of particular interest was that the impact of ITC was similar to the impact or micrometastases.