Missed micrometastatic disease in breast cancer

In the era of sentinel lymph node (SLN) biopsy for breast cancer, ultrastaging by enhanced pathologic techniques (serial sections and/or immunohistochemical [IHC] staining) has become logistically feasible for the first time. Retrospective studies suggest that SLN (and bone marrow) micrometastases detected by these methods are prognostically significant, but controversy still surrounds the significance of micrometastases detected only by IHC, and especially of isolated tumor cells. This heterogeneity among micrometastases may confound the interpretation of current prospective clinical trials that aim to determine their significance. A major challenge for future investigations will be to determine if SLN and bone marrow micrometastases represent similar or distinct biologic phenomena, and whether this distinction will have any implications for treatment.