ABSTRACT
PURPOSE: We aimed to examine the association between alterations in multidrug resistance (MDR) gene expression, measured before and after neoadjuvant chemotherapy (NAC), and short-term response in a cohort of stage IIA-IIIC breast cancer patients (n = 84). METHODS: All patients were treated with two to four preoperative cycles of FAC (5-fluorouracil-adriamycin-cyclophosphamide), CAX (cyclophosphamide-adriamycin-xeloda) or taxane regimes. The expression levels of key MDR genes (ABCB1, ABCC1, ABCC2, ABCC3, ABCC5, ABCG1, ABCG2, GSTP1, and MVP) were evaluated in both tumor tissues obtained pre-therapy and in specimens removed by final surgery, using TaqMan-based quantitative reverse transcriptase PCR. RESULTS: No significant difference in the average level of MDR gene expression in paired breast tumors before and after NAC was found when analyzed in both responsive and non-responsive patients. There was no correlation between the expression levels of MDR genes in pre-NAC tumors and immediate NAC response. In the group with tumor responses, we found a statistically significant downregulation of expression of ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2, GSTP1, and MVP genes following NAC in FAC and CAX-treated patients (67-93% of cases). In contrast, we found that expression of these genes was upregulated after NAC, mostly in non-responsive patients (55-96% of cases). Responsiveness to taxotere was related to reduced levels of ABCB1, ABCC2, ABCG1, ABCG2, and MVP mRNA in tumor samples collected after chemotherapy. CONCLUSION: Our results suggest that reductions in MDR gene expression in post-NAC samples in comparison with pre-NAC are associated with tumor response to FAC and CAX as well as taxotere-based NAC, while patients displaying MDR gene upregulation had resistance to therapy.
