Molecular and Cellular Biochemistry

, Volume 444, Issue 1–2, pp 197–206 | Cite as

Predictive value of vascular endothelial growth factor receptor type 2 in triple-negative breast cancer patients treated with neoadjuvant chemotherapy

  • Nataliya Babyshkina
  • Marina Zavyalova
  • Natalia Tarabanovskaya
  • Tatyana Dronova
  • Nadejda Krakhmal
  • Elena Slonimskaya
  • Julia Kzhyshkowska
  • Evgeny Choynzonov
  • Nadejda Cherdyntseva
Article
  • 156 Downloads

Abstract

The identification of informative biomarkers that could predict the treatment response is particularly important in the triple-negative (TN) breast cancer, which is characterized by biological diversity. The aim of this study was to investigate the impact of vascular endothelial growth factor receptor (VEGFR2) expression and its gene polymorphisms on pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) in Russian patients with TN breast cancer. We performed a retrospective analysis of 70 women with operable TN breast cancer, who underwent NCT with 5-fluorouracil, adriamycin, and cyclophosphamide (FAC) or cyclophosphamide, adriamycin, and capecitabine (CAX) between 2007 and 2013. VEGFR2 expression was evaluated before NCT by immunohistochemistry. TaqMan SNP assays were used for genotyping KDR − 604T>C (rs2071559) and KDR 1192G>A (rs2305948) polymorphisms. The pCR was used as an end-point in the treatment efficacy analysis. In the univariate analysis, the pCR rate was strongly associated with young age (P = 0.004), high Ki67 expression (P = 0.012), lymph node negativity (P = 0.023) as well as with positive VEGFR2 expression (P = 0.019) and the CAX regimen (P = 0.005). In the multivariate analysis, only patient’s age (P = 0.005) and pre-NCT VEGFR2 expression (P = 0.048) remained significant predictors of pCR. The pCR rate was higher in the CAX-treated patients than that in the FAC-treated patients (P = 0.005). Our results revealed that − 604TT genotype of rs2071559 and age < 50 years were correlated with a pCR in the CAX-treated patients. VEGFR2 expression in pre-NCT tumors and KDR gene polymorphism can be considered as additional predictive molecular markers of pCR in Russian TN breast cancer patients treated with NCT.

Keywords

Triple-negative breast cancer Neoadjuvant chemotherapy Pathologic complete response Vascular endothelial growth factor receptor (VEGFR2) Gene polymorphisms Predictive markers 

Notes

Acknowledgements

The study was supported by the ERA Net RUS Plus S&T CHIT-ALPHA-THER grant, the Russian Foundation for Basic Research (Project No. 16-54-76015). We acknowledge support of this work by the Tomsk State University Competitiveness Improvement Program. We are grateful to Dr. Viktoriya Stalbovskaya and Dr. Matvey Tsyganov for assistance with statistical analysis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Nataliya Babyshkina
    • 1
    • 4
  • Marina Zavyalova
    • 3
    • 4
    • 5
  • Natalia Tarabanovskaya
    • 2
  • Tatyana Dronova
    • 1
    • 4
  • Nadejda Krakhmal
    • 3
    • 5
  • Elena Slonimskaya
    • 2
    • 5
  • Julia Kzhyshkowska
    • 4
    • 6
  • Evgeny Choynzonov
    • 7
  • Nadejda Cherdyntseva
    • 1
    • 4
    • 5
  1. 1.Department of Molecular Oncology and Immunology, Federal State Budgetary Scientific Institution “Саncеr Research Institute”, Tomsk National Research Medical CenterRussian Academy of SciencesTomskRussian Federation
  2. 2.Department of General Oncology, Federal State Budgetary Scientific Institution “Cаncеr Research Institute”, Tomsk National Research Medical CenterRussian Academy of SciencesTomskRussian Federation
  3. 3.Department of Pathological Anatomy and Cytology, Federal State Budgetary Scientific Institution “Саncеr Research Institute”, Tomsk National Research Medical CenterRussian Academy of SciencesTomskRussian Federation
  4. 4.Department of Translational Cellular and Molecular BiomedicineNational Research Tomsk State UniversityTomskRussian Federation
  5. 5.Department of General OncologySiberian State Medical UniversityTomskRussian Federation
  6. 6.Institute of Transfusion Medicine and ImmunologyMedical Faculty Mannheim University of HeidelbergMannheimGermany
  7. 7.Federal State Budgetary Scientific Institution “Саncеr Research Institute”, Tomsk National Research Medical CenterRussian Academy of SciencesTomskRussian Federation

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