Clinical significance of sentinel lymph node isolated tumour cells in breast cancer.

The advent of sentinel lymph node biopsy (SLNB) and improvements in histopathological and molecular analysis have increased the rate at which isolated tumour cells (ITC) are identified. However, their biological and clinical significance has been the subject of much debate. In this article we review the literature concerning SLNB with particular reference to ITC. The controversies regarding histopathological assessment, clinical relevance and management implications are explored. The literature review was facilitated by Medline, PubMed, Embase and Cochrane databases. Published studies have reported divergent results regarding the biological significance and clinical implications of ITC in general and SLN ITC in particular. Some studies demonstrate no associations, whilst others have found these to be indicators of poor prognosis, associated with non-SLN involvement, in addition to local recurrence and distant disease. Absolute consensus regarding the optimal analytical technique for SLN has yet to be reached, particularly concerning immunohistochemical (IHC) techniques targeting cytokeratins and contemporary molecular analysis. The clinical relevance of ITC within the SLN should be primarily determined by the magnitude of their impact on patient management and outcome measures. The modest up-staging within current classification systems is justified and reflects the marginally poorer prognosis for women with SLN ITC. Management need not be altered where further axillary treatment with surgical clearance or radiotherapy and systemic adjuvant treatment are already indicated. However, in the absence of level-1 guidance, each case requires discussion with regard to other tumour and patient related factors in the context of the multidisciplinary team. The identification of ITC remains highly dependent on the analytical technique employed and there exists potential for stage migration and impact on management decisions. Evidence supporting the routine analysis of deeper tissue sections by IHC is lacking and molecular technologies should be restricted to research purposes at present.