Changing the expression vector of multidrug resistance genes is related to neoadjuvant chemotherapy response.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Experimental Oncology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation.
Nicolay V
NV
Litviakov
Nadezhda V
NV
Cherdyntseva
Matvey M
MM
Tsyganov
Evgeny V
EV
Denisov
Evgeny Y
EY
Garbukov
Marina K
MK
Merzliakova
Victor V
VV
Volkomorov
Sergey V
SV
Vtorushin
Marina V
MV
Zavyalova
Elena M
EM
Slonimskaya
Vladimir M
VM
Perelmuter
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D020360:Neoadjuvant Therapy / Q000379:methods; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects
C000715087:ABCC2 protein, human; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2