Influence of a Dose-dense Adjuvant Chemotherapy on sVCAM-1/sICAM-1 Serum Levels in Breast Cancer Patients with 1-3 Positive Lymph Nodes HOLM EGGEMAN1, FRANK STÖBLEN2, MARC THILL3, SUSANNE KORLACH†, PETER SCHMID4, DIANA LÜFTNER5, DIRK ELLING6, FLORIN-ANDREI TARAN1, SHERKO KÜMMEL7 and SOLVEIG LANDT8

Background/Aim: The aim of the present study was to investigate the effects of conventional and dosedense chemotherapy on serum levels of soluble adhesion molecules sICAM-1 and sVCAM-1 in node-positive patients with breast cancer. Patients and Methods: sICAM-1 and sVCAM-1 were measured in the blood serum of 147 patients with breast cancer and with 1 to 3 affected lymph nodes prior to and after conventional or dose-dense chemotherapy within a randomized phase III study (NOGGO trial). Results: The increase in sICAM-1 (p<0.0001) and sVCAM-1 (p<0.001) levels after chemotherapy was statistically significant within the entire sample and the dose-dense study arm. sVCAM-1 levels were not altered by conventional chemotherapy, but were markedly and significantly increased after the dose-dense regimen. Higher sICAM-1 concentrations were found in postmenopausal patients, and the difference was significant before, but not after treatment. There was no significant correlation with other prognostic criteria. Conclusion: Both sVCAM-1 and sICAM-1 levels changed significantly after adjuvant chemotherapy, the effect being more marked under the dose-dense regimen. The possible prognostic relevance of adhesion molecule concentration and the effect of different modes of chemotherapy remains to be determined. Growth and dissemination of tumors are the result of a variety of processes, such as uncontrolled cell proliferation, loss of homophilic cell-to-cell contacts, migration of malignant cells into blood and lymphatic vessels, interaction with white blood cell (WBC) and platelet surface structures, and induction of neo-angiogenesis and their mutual interrelationships (1, 2) Intercellular adhesion molecules play a key role in the facilitation of tumor invasion and dissemination. This group consists of selectins, integrins and cadherins, as well as intercellular adhesion molecule 1 (ICAM-1) and vascular adhesion molecule 1 (VCAM-1). The latter are cell surface glycoproteins that belong to the immunoglobulin superfamily and whose expression and activity is enhanced in inflammation. Their biologic function is an interaction with integrins that results in the formation of cell connections which in turn promote the adhesion and diapedesis of WBCs (3-6). Via these mechanisms, ICAM-1/VCAM-1 appear to be involved in tumor cell adhesion to vascular endothelial cells, an important pathway of tumor dissemination and metastasis formation. In the 1990s, soluble species of these adhesion molecules (sICAM-1/sVCAM-1) have been described (7-10), and an increase in their serum concentrations was found in patients with colorectal (11) and gastric cancer (12). In breast cancer patients, increased serum concentrations of sICAM-1 were described, and their level seems to be related to poorer therapy response and prognosis (13, 14); however, these findings are not conclusive in the literature (9).