Expression of multidrug resistance gene 1 (MDR1) and its association with development and clinical outcome of breast carcinoma
Abstract
Background: Multiple drug resistance presents a major problem for successful cancer chemotherapy. One of the most important proteins contributing to the development of resistance is the P-glycoprotein encoded by multidrug resistance gene 1 (MDR1, newly ABC-B1).
A high expression of MDR1 might correlate with shorter overall survival and worse chemotherapy outcome. Methods: mRNA levels of MDR1 were analyzed in 88 breast tumor samples and in adjacent non-tumor tissue samples (n = 40) by real-time PCR.
Statistical comparisons between the levels of MDR1 expression and clinical-pathological data were performed using ANOVA test. Kaplan-Meier's statistics test was used for the estimation of significance of differences in overall and disease-free survivals.
Results: MDR1 was expressed in 87/88 (98,9 %) of tumors samples and in 39/40 (97,5%) of non-tumor breast samples. Striking inter-individual variability in expression of MDR1 was found with down-regulation in almost 89,7% of all tumors.
No correlation of MDR1 expression with clinical-pathological characteristics was found. Patients with high MDR1 expression treated with P-gp substratess anthracycline or taxane containing regimens had significantly shorter disease-free survival than those treated by other regimens (P = 0,031).
Conclusion: MDR1 expression seems appears to be a potential predictive factor of chemotherapy outcome in breast cancer patients treated with anthracycline or taxane containing regimens.