title: 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.
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.
authors.affiliation: Department of Molecular Oncology and Immunology, Federal State Budgetary Scientific Institution "Tomsk Cancer Research Institute", 5 Kooperativny Street, Tomsk, Russian Federation, 634050. nbabyshkina@mail.ru.|Department of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, Tomsk, Russian Federation, 634050. nbabyshkina@mail.ru.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Babyshkina
authors.affiliation: Department of Pathological Anatomy and Cytology, Federal State Budgetary Scientific Institution "Tomsk Cancer Research Institute", Tomsk, Russian Federation, 634050.|Department of General Oncology, Siberian State Medical University, Tomsk, 634050, Russian Federation.
authors.forename: Sergey
authors.initials: S
authors.lastname: Vtorushin
authors.affiliation: Department of Pathological Anatomy and Cytology, Federal State Budgetary Scientific Institution "Tomsk Cancer Research Institute", Tomsk, Russian Federation, 634050.|Department of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, Tomsk, Russian Federation, 634050.|Department of General Oncology, Siberian State Medical University, Tomsk, 634050, Russian Federation.
authors.forename: Marina
authors.initials: M
authors.lastname: Zavyalova
authors.affiliation: Department of General Oncology, Federal State Budgetary Scientific Institution "Tomsk Cancer Research Institute", Tomsk, Russian Federation, 634050.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Patalyak
authors.affiliation: Department of Molecular Oncology and Immunology, Federal State Budgetary Scientific Institution "Tomsk Cancer Research Institute", 5 Kooperativny Street, Tomsk, Russian Federation, 634050.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Dronova
authors.affiliation: Department of Molecular Oncology and Immunology, Federal State Budgetary Scientific Institution "Tomsk Cancer Research Institute", 5 Kooperativny Street, Tomsk, Russian Federation, 634050.|Department of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, Tomsk, Russian Federation, 634050.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Litviakov
authors.affiliation: Department of General Oncology, Federal State Budgetary Scientific Institution "Tomsk Cancer Research Institute", Tomsk, Russian Federation, 634050.|Department of General Oncology, Siberian State Medical University, Tomsk, 634050, Russian Federation.
authors.forename: Elena
authors.initials: E
authors.lastname: Slonimskaya
authors.affiliation: Department of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, Tomsk, Russian Federation, 634050.|Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim University of Heidelberg, 68167, Mannheim, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Kzhyshkowska
authors.affiliation: Department of Molecular Oncology and Immunology, Federal State Budgetary Scientific Institution "Tomsk Cancer Research Institute", 5 Kooperativny Street, Tomsk, Russian Federation, 634050.|Department of Translational Cellular and Molecular Biomedicine, National Research Tomsk State University, Tomsk, Russian Federation, 634050.|Department of General Oncology, Siberian State Medical University, Tomsk, 634050, Russian Federation.
authors.forename: Nadejda
authors.initials: N
authors.lastname: Cherdyntseva
authors.affiliation: Federal State Budgetary Scientific Institution "Tomsk Cancer Research Institute", Tomsk, Russian Federation, 634050.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Choynzonov
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D047628:Estrogen Receptor alpha / Q000032:analysis* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D014644:Genetic Variation; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D017978:Receptors, Growth Factor / Q000032:analysis* / Q000235:genetics; D012426:Russia; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D017978:Receptors, Growth Factor; D013629:Tamoxifen
keywords: Breast cancer; EGFR expression; ERα expression; Prognosis markers; Single-nucleotide polymorphisms; Tamoxifen resistance