Despite apparent curative surgery in the treatment of breast cancer, 21% of node-negative patients still develop lymph node and distant metastatic disease at 18 years. It is likely that this group of patients has occult micrometastatic disease at the time of initial surgery, and that they are understaged. Recent studies have established that current routine histological assessment of regional lymph nodes underestimates breast cancer metastases. Use of serial sectioning and immunohistochemistry for the evaluation of routine histology-negative lymph nodes in patients with breast cancer has been performed in multiple studies and been shown to increase the detection rate of micrometastatic disease by 9% to 31%. However, the growth properties and of human breast cancer micrometastases remain unknown and their significance obscure.

The commonly accepted theory of breast cancer metastatic development, Gompertzian growth kinetics, assumes that neoplastic growth begins with tumor seeding and continues until clinical recurrence is documented. This theory postulates that near-regular exponential growth occurs at small cell numbers than larger tumors, but also have more cells in their mitotic cycle and are thus more susceptible to chemotherapy. This model has been the basis of conventional chemotherapy.

An alternate way to explain breast cancer metastatic development is the tumor dormancy hypotheses. This hypothesis assumes that, for some patients during the pre-clinical phase, micrometastases do not grow for a given period of time, depending on tumor and/or host factors. The immune system and suppression of angiogenesis are the most likely of various possible causes of this phenomenon. Micrometastases may eventually escape dormancy when a subset of tumor cells within the micrometastases switching to an angiogenic occurs, dormancy is broken, tumor proliferation increases, and clinically evident metastatic disease develops.

Tumor dormancy has been documented in animal tumor models where micrometastatic foci have been directly observed and studied. These studies have shown that inhibition of vascularization of these micrometastases might explain how some tumor cells remain dormant. Animal studies have demonstrated that micrometastatic cells are dependent on passive diffusion for oxygen and nutrient supply, and this may limit their growth to 2 to 3 mm. To grow larger than a few cubic millimeters, solid tumors must generate new vasculature through the process of angiogenesis. In mice, lung metastases, dormant during angiogenesis suppression with angiostatin, exhibited rapid growth when the inhibition of angiogenesis was removed.

In the past decade, our ability to detect occult breast cancer micrometastases has been enhanced by the advent of sentinel lymph node biopsy, and therefore breast cancer micrometastatases are more readily available to study. The sentinel lymph node technique focuses on the first node in the lymphatic basin, the ‘sentinel’ node, which, as the first node to receive drainage from the tumor site, is the regional node most likely to harbor metastatic disease. The use of serial sectioning and immunohistochemistry for the evaluation of routine histologically negative lymph nodes in patients with breast cancer has been the subject of multiple studies and increases the detection rate of micrometastatic disease by 9%-31%. Therefore, sentinel lymphadenectomy with serial sectioning and immunohistochemistry provides a novel way to obtain specimens of breast micrometastases for laboratory investigation.