Montagna E, Viale G, Rotmensz N et al.
European Institute of Oncology, Milan, Italy.
Breast Cancer Res Treat 2009;118:385–94.
Editor’s note: Sentinel lymph node biopsy (SLNB) has been widely adopted as a minimally invasive staging procedure that avoids the morbidity associated with more extensive axillary lymph node dissection (ALND). Intense debate followed the pioneering work of Armando Giuliano (
Ann Surg 1997;226:271–6), David Krag (
N Engl J Med 1998;339:941–6), and Umberto Veronesi (
Lancet 1997;349:1864–7) with regard to the risk of false-negatives – the fear that unsuspected involved lymph nodes would be left behind and patients would be understaged. The pathologist workload shifted: routine hematoxylin–eosin examination of one or two slices with a large number of lymph nodes removed by ALND was traded for intense scrutiny using multiple serial sectioning aided by immunohistochemistry of a smaller number of lymph nodes removed by SLNB. Intuitively, this made sense in order to reduce the risk of false-negatives; if intensive workup of the SLNs failed to detect tumoral cells, then it would be unlikely that other lymph nodes left behind would be involved. However, early on, Blake Cady questioned the meaning of discovering micrometastases or a few cytokeratin-positive cells in a single lymph node, remarking that such a discovery may accomplish no more than stage shifting, and questioning whether it is a good thing if a node-negative patient with an excellent prognosis is made node-positive and given adjuvant therapy (
Ann Surg 1997;226:276–7). These concerns remain acutely relevant. Stage migration has been shown to occur; women diagnosed in 2003–2005 have been found to have a 3.5-fold higher risk of having micrometastases compared with women diagnosed in 1994–1995, as a consequence of intensified pathological processing (
Breast Cancer Res Treat 2009;113:173–9). In a recent population-based study pooling 2707 patients from 113 hospitals, adjuvant therapy was associated with improved 5-year disease-free survival (DFS) rates in women with favorable early stage breast cancer who presented with isolated tumor cells (ITCs) or micrometastases in regional lymph nodes(
N Engl J Med 2009;361:653–63).