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The distribution pattern of ERα expression, ESR1 genetic variation and expression of growth factor receptors: association with breast cancer prognosis in Russian patients treated with adjuvant tamoxifen

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Abstract

Identification of additional biomarkers associated with ER genomic and nongenomic pathways could be very useful to distinguish patients who will benefit from tamoxifen treatment. The aim of this study was to analyze the prognostic significance of the distribution pattern of ERα expression, ESR1 gene single-nucleotide polymorphisms and expression levels of growth factor receptors in Russian hormone receptor-positive breast cancer patients treated with adjuvant tamoxifen. Formalin-fixed paraffin-embedded tumor tissue samples from 97 patients were examined for the distribution pattern of ERα expression, as well as for EGFR and TGF-βR1 expression by immunohistochemistry. Genotypes for ESR1 +30T>C (rs2077647) and ESR1 2014G>A (rs2228480) were analyzed using a TaqMan assay. Progression-free survival (PFS) was used as an endpoint for the survival analyses. We found that patients with the heterogeneous distribution of ERα expression had poor prognosis on tamoxifen treatment (P = 0.021). We identified a high EGFR expression in patients who developed distant metastasis or recurrence during tamoxifen treatment (a tamoxifen-resistant group—TR) in contrast to the distant metastasis-free patients (a tamoxifen-sensitive group—TS) (80.0 vs. 41.9 %, respectively, P = 0.009). Carriers of the ESR12014A mutant allele were more prevalent among the TR patients compared to the TS patients (26.3 vs. 8.0 %, respectively, P = 0.009). EGFR expression and the distribution pattern of ERα expression were associated with the response to tamoxifen by both univariate and multivariate logistic regression analyses. The presence of these markers either alone or in combination was correlated with the worse PFS for all patients. Analysis of the distribution pattern of ERα expression and the EGFR status in tumor tissue may be valuable for patient selection for tamoxifen adjuvant therapy.

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Acknowledgments

The study was supported by the Russian Scientific Foundation, Grant #14-15-00350 (tumor sample collection, clinical data for patients within follow-up period). We acknowledge support of this work by the Tomsk State University Competitiveness Improvement Program.

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Authors and Affiliations

  1. Department of Molecular Oncology and Immunology, Federal State Budgetary Scientific Institution “Tomsk Cancer Research Institute”, 5 Kooperativny Street, Tomsk, Russian Federation, 634050

    Nataliya Babyshkina, Tatyana Dronova, Nikolay Litviakov & Nadejda Cherdyntseva

  2. Department of General Oncology, Federal State Budgetary Scientific Institution “Tomsk Cancer Research Institute”, Tomsk, Russian Federation, 634050

    Stanislav Patalyak & Elena Slonimskaya

  3. Department of Pathological Anatomy and Cytology, Federal State Budgetary Scientific Institution “Tomsk Cancer Research Institute”, Tomsk, Russian Federation, 634050

    Sergey Vtorushin & Marina Zavyalova

  4. Department of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, Tomsk, Russian Federation, 634050

    Nataliya Babyshkina, Marina Zavyalova, Nikolay Litviakov, Julia Kzhyshkowska & Nadejda Cherdyntseva

  5. Department of General Oncology, Siberian State Medical University, Tomsk, 634050, Russian Federation

    Sergey Vtorushin, Marina Zavyalova, Elena Slonimskaya & Nadejda Cherdyntseva

  6. Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim University of Heidelberg, 68167, Mannheim, Germany

    Julia Kzhyshkowska

  7. Federal State Budgetary Scientific Institution “Tomsk Cancer Research Institute”, Tomsk, Russian Federation, 634050

    Evgeny Choynzonov

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  1. Nataliya Babyshkina
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Correspondence to Nataliya Babyshkina.

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Ethical statement

The study was approved by the Ethics Committee of the Tomsk Cancer Research Institute and has been performed in accordance with the Helsinki Declaration (1964, amended in 1975 and 1983).

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

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Babyshkina, N., Vtorushin, S., Zavyalova, M. et al. The distribution pattern of ERα expression, ESR1 genetic variation and expression of growth factor receptors: association with breast cancer prognosis in Russian patients treated with adjuvant tamoxifen. Clin Exp Med 17, 383–393 (2017). https://doi.org/10.1007/s10238-016-0428-z

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  • DOI: https://doi.org/10.1007/s10238-016-0428-z

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