Breast cancer: Pretreatment drug resistance parameters (GSH-system, ATase, P-glycoprotein) in tumor tissue and their correlation with clinical and prognostic characteristics

Buser, K.; Joncourt, F.; Altermatt, H.J.; Bacchi, M.; Oberli, A.; Cerny, Th. (1997). Breast cancer: Pretreatment drug resistance parameters (GSH-system, ATase, P-glycoprotein) in tumor tissue and their correlation with clinical and prognostic characteristics. Annals of oncology, 8(4), pp. 335-341. Kluwer Academic Publishers 10.1023/A:1008202723066

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Background: The identification of new factors predicting relapse, outcome and response to systemic therapy in breast cancer is warranted. The measurement of biological markers such as drug resistance parameters (DRPs), which are part of the phenotype of malignant cells and contribute to resistance to anti-cancer drugs may be a possibility, which may ultimately lead to improvement of therapeutic results.

Patients and methods: The level of glutathione (GSH), activities of glutathione-S-transferase (GST), glutathione-peroxidase (GPx), 06-alkylguanine-DNA-alkyltransferase (ATase), and P-glycoprotein (PGP) were measured in tumor and adjacent tumor free tissue samples from 89 consecutive, untreated females with breast cancer and correlated with clinical and prognostic factors. Early breast cancer (EBC) was diagnosed in 56 patients, 22 patients had locally advanced (LABC) and 11 patients metastatic breast cancer.

Results: All DRPs showed significantly higher expression in tumor than 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 well as in normal tissue. GST activity was significantly higher in EBC than in LABC or metastatic breast cancer (P = 0.02). GSH level was significantly higher in grade I 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 apparent between groups of ‘high’ and ‘low’ DRP-expression. However, the 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 initial phenotype of the malignant cells. Due to its high prevalence (83% in EBC, 100% in primarily metastatic breast cancer), PGP did not add to prognostic information. High levels of GSH, GST and and GPx were associated with favorable clinical characteristics and good prognosis, whereas low levels of GSH and GST activity were associated with more aggressive or more advanced disease.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Altermatt, H.J. and Cerny, Thomas

ISSN:

0923-7534

Publisher:

Kluwer Academic Publishers

Language:

English

Submitter:

Marceline Brodmann

Date Deposited:

27 Aug 2020 10:39

Last Modified:

27 Aug 2020 10:39

Publisher DOI:

10.1023/A:1008202723066

BORIS DOI:

10.7892/boris.114964

URI:

https://boris.unibe.ch/id/eprint/114964

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