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

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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.

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Acknowledgments

This work was supported by the Federal Target Program "Academic and Teaching Staff of Innovative Russia in 2009–2013" (#16.740.11.0606 and #8291) of the Ministry of Education and Science of the Russian Federation, the Russian Federation President Grant (#MK-1259.2012.7), and a grant from the OPTEK company (#1/11KTS).

Conflict of interest

The other authors have no conflicts of interest.

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Authors and Affiliations

  1. Department of Experimental Oncology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, 634050, Russian Federation

    Nicolay V. Litviakov, Nadezhda V. Cherdyntseva, Matvey M. Tsyganov, Evgeny V. Denisov, Marina K. Merzliakova & Victor V. Volkomorov

  2. Department of Oncology, Siberian State Medical University, Tomsk, Russian Federation

    Nadezhda V. Cherdyntseva & Elena M. Slonimskaya

  3. Department of General Oncology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation

    Evgeny Y. Garbukov & Elena M. Slonimskaya

  4. Department of Pathological Anatomy and Cytology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation

    Sergey V. Vtorushin, Marina V. Zavyalova & Vladimir M. Perelmuter

  5. Department of Pathological Anatomy, Siberian State Medical University, Tomsk, Russian Federation

    Sergey V. Vtorushin, Marina V. Zavyalova & Vladimir M. Perelmuter

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  1. Nicolay V. Litviakov
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  2. Nadezhda V. Cherdyntseva
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  3. Matvey M. Tsyganov
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  8. Sergey V. Vtorushin
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  9. Marina V. Zavyalova
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  10. Elena M. Slonimskaya
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Correspondence to Nadezhda V. Cherdyntseva.

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Litviakov, N.V., Cherdyntseva, N.V., Tsyganov, M.M. et al. Changing the expression vector of multidrug resistance genes is related to neoadjuvant chemotherapy response. Cancer Chemother Pharmacol 71, 153–163 (2013). https://doi.org/10.1007/s00280-012-1992-x

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