Clinical outcome of patients with lymph node‐negative breast carcinoma who have sentinel lymph node micrometastases detected by immunohistochemistry

Abstract

We read with great interest the article by Chagpar et al. and congratulate the authors.1 We agree that micrometastases do not affect the outcomes significantly in patients with breast carcinoma. At the same time, a fundamental problem in cancer research is the identification of the cell type capable of sustaining the growth of the neoplastic clone. There is overhelming evidence that virtually all tumors are clonal and represent the progeny of a single cell. Two theories were developed to explain why not every cell within a tumor is capable of regenerating the tumor. The stochastic theory predicts that every tumor cell is potentially tumor initiating but that entry into the cell cycle is governed by low-probability stochastic events. Conversely, the hierarchy theory proposes that the tumor is functionally heterogeneous and that only a limited number of cells are capable of initiating the tumor.2 Al-Hajj et al. provided a major step forward with the identification of human breast carcinoma-initiating cells. The authors found that only a minority of breast carcinoma cells had the ability to form new tumors. They prospectively identified and isolated the tumorigenic cells as CD44(+)CD24(-/low)Lineage(-) in eight of nine patients.3 The ability to seperate tumorigenic and nontumorigenic populations of tumor cells should allow the molecular characterization of these cells and the elucidation of the pathways that account for their tumorigenic potential. Furthermore, the existence of a subset of tumorigenic cells within a tumor would provide an explanation for a number of clinical observations made in breast carcinoma patients. For example, it has been demonstrated that up to 30% of breast carcinoma patients may demonstrate micrometastatic disease in their bone marrow at the time of presentation. However, after 5 years, only 50% of these patients will demonstrate clinically evident metastases. This finding has been speculated to be the result of tumor dormancy. An alternative explanation is that the disseminated tumor cells in this group of patients arose from the spread of nontumorigenic cells, and only when tumor stem cells disseminate and subsequently self-renew will metastatic tumors form. This second explanation suggests that the development of diagnostic reagents that allow for the prospective identification of tumorigenic cells may have prognostic significance for patients with breast carcinoma.3 Mesult Tez M.D.*, Selda Tez M.D.*, * Ataturk Chest Diseases, Research Hospital, Ankara, Turkey