ISSN:
1569-8041
Keywords:
ATase
;
breast cancer
;
drug resistance
;
PGP
;
GPx
;
GSH
;
GST
;
prognosis
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Background: The identification of new factors predicting relapse,outcome and response to systemic therapy in breast cancer is warranted. Themeasurement of biological markers such as drug resistance parameters (DRPs),which are part of the phenotype of malignant cells and contribute toresistance to anti-cancer drugs may be a possibility, which may ultimatelylead to improvement of therapeutic results. Patients and methods: The level of glutathione (GSH), activities ofglutathione-S-transferase (GST), glutathione-peroxidase (GPx),06-alkylguanine-DNA-alkyltransferase (ATase), and P-glycoprotein (PGP) weremeasured in tumor and adjacent tumor free tissue samples from 89 consecutive,untreated females with breast cancer and correlated with clinical andprognostic factors. Early breast cancer (EBC) was diagnosed in 56 patients,22 patients had locally advanced (LABC) and 11 patients metastatic breastcancer. Results: All DRPs showed significantly higher expression in tumorthan in tumor free tissues. GPx was positively correlated with GST (R = 0.3, P = 0.0048) and with GSH (R = 0.5, P = 0.0001) in tumor as wellas in normal tissue. GST activity was significantly higher in EBC than in LABCor metastatic breast cancer ( P = 0.02). GSH level was significantlyhigher in grade 1 than in grade 2 or grade 3 tumors ( P = 0.01). Whenclinical characteristics were related to the level of DRP, ‘high’ GSH wasassociated with age 〉60 years ( P = 0.01) in EBC, and with grade1–2 tumors ( P = 0.05) in LABC. No differences in OS were apparentbetween groups of ‘high’ and ‘low’ DRP-expression. However, the four-yearestimated 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 ofbreast cancer patients are part of the initial phenotype of the malignantcells. Due to its high prevalence (83% in EBC, 100% in primarilymetastatic breast cancer), PGP did not add to prognostic information. Highlevels of GSH, GST and and GPx were associated with favorable clinicalcharacteristics and good prognosis, whereas low levels of GSH and GST activitywere associated with more aggressive or more advanced disease.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008202723066
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