Addition of granulocyte-colony stimulating factor (G-CSF) to adjuvant treatment may increase survival in patients with operable breast cancer: interaction of G-CSF with dormant micrometastatic breast cancer cells

All cancers are clonal and represent the progeny of a single cell. The unclear point is which clonogenic cells within the tumor clone possess tumor-initiating cell (T-IQ function and are capable of maintaining tumor growth. Stem cells have the ability to divide almost indefinitely. The division can give rise to a new stem cell as well as differentiated cells of the tumor. Breast tumors are comprised of phenotypically diverse populations of breast cancer cells. Among them, the breast cancer stem cell is important for regrowth of tumor and metastasis. Granulocyte-colony stimulating factor (G-CSF) stimulates the pluripotent stem cell beside neutrophil precursors. Breast cancer stem cells which have not been characterized totally may carry the almost identical antigens with hematopoietic stem cell. The dose-intense therapies with the addition of G-CSF in the adjuvant treatment of breast cancer improved clinical outcomes significantly. Presence of micrometastasis in bone marrow of the breast cancer patients is predictor of relapse free survival and important prognostic factor. Actually, breast cancer stem cells in the thousands of micrometastatic cancer cells have the capacity to repopulate and metastasise. We hypothesize that G-CSF use in adjuvant treatment of breast cancer may activate and repopulate these dormant breast cancer stem cells besides its stimulation on blood stem cells. So activated breast cancer stem cells become chemosensitive to cell-cycle specific various chemotherapeutic agents. Improvement in overall survival in operable breast cancer patients having been treated by dose-dense therapies may also be explained by this mechanism. (C) 2004 Elsevier Ltd. All rights reserved.