BREAST-CANCER - PRETREATMENT DRUG-RESISTANCE PARAMETERS (GSH-SYSTEM, ATASE, P-GLYCOPROTEIN) IN TUMOR-TISSUE AND THEIR CORRELATION WITH CLINICAL AND PROGNOSTIC CHARACTERISTICS

Background. The identification of new factors predicting relapse, outc ome and response to systemic therapy in breast cancer is warranted. Th e measurement of biological markers such as drug resistance parameters (DRPs), which are part of the phenotype of malignant cells and contri bute to resistance to anti-cancer drugs may be a possibility, which ma y ultimately lead to improvement of therapeutic results. Patients and methods. The level of glutathione (GSH), activities of glutathione-S-t ransferase (GST), glutathione-peroxidase (GPx), 06-alkylguanine-DNA-al kyltransferase (ATase), and P-glycoprotein (PGP) were measured in tumo r and adjacent tumor free tissue samples from 89 consecutive, untreate d females with breast cancer and correlated with clinical and prognost ic factors. Early breast cancer (EBC) was diagnosed in 56 patients, 22 patients had locally advanced (LABC) and 11 patients metastatic breas t cancer. Results. All DRPs showed significantly higher expression in tumor than in tumor free tissues. GPx was positively correlated with G ST (r = 0.3, P = 0.0048) and with GSH (r = 0.5, P = 0.0001) in tumor a s well as in normal tissue. GST activity was significantly higher in E BC than in LABC or metastatic breast cancer (P = 0.02). GSH level was significantly higher in grade 1 than in grade 2 or grade 3 tumors (P = 0.01). When clinical characteristics were related to the level of DRP , 'high' GSH was associated with age > 60 years (P = 0.01) in EBC, and with grade 1-2 tumors (P = 0.05) in LABC. No differences in OS were a pparent between groups of 'high' and 'low' DRP-expression. However, th e four-year estimated disease-free survival of EBC tended to be higher in patients with 'high' GST (P = 0.10) and of LABC in patients with ' high' GPx levels (P = 0.06).Conclusion: We conclude that 'high' levels of DRP in tumor tissue of breast cancer patients are part of the init ial phenotype of the malignant cells. Due to its high prevalence (83% in EBC, 100% in primarily metastatic breast cancer), PGP did not add t o prognostic information. High levels of GSH, GST and and GPx were ass ociated with favorable clinical characteristics and good prognosis, wh ereas low levels of GSH and GST activity were associated with more agg ressive or more advanced disease.