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Impact of estrogen receptor α on the tamoxifen response and prognosis in luminal-A-like and luminal-B-like breast cancer

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Abstract

The luminal-A-like and luminal-B-like breast cancer groups have distinct biological features that lead to differences in the treatment response and clinical outcome. The aim of this study was to examine the value of the distribution pattern of ERα expression, ESR1 SNPs as well as ESR1 mRNA expression in predicting tamoxifen response and survival in patients with luminal-A-like and luminal-B-like breast cancer. A total of 135 patients with both subtypes were stratified into two groups depending on the tamoxifen response: tamoxifen-resistant patients (TR) and tamoxifen-sensitive patients (TS). ESR1 mRNA expression was measured by real-time quantitative reverse transcription-PCR. Three polymorphisms of ESR1 (rs2077647, rs2228480 and rs1801132) were genotyped using a TaqMan assay. The distribution pattern of ERα expression was analyzed immunohistochemically using the visual assessment of staining. The primary endpoint was progression-free survival (PFS). There was a significant decrease in ESR1 mRNA expression level in the TR group when compared to the TS group among patients with luminal-B-like subtype (P = 0.038). ESR1 2014AA mutant genotype of rs2228480 was more prevalent in the TR patients with luminal-B-like subtype than the TS group (P = 0.045). In the luminal-A-like group, tamoxifen-resistant tumors were more frequently heterogeneous for ERα expression than tamoxifen-sensitive tumors (P = 0.016). Multivariate analysis showed a strong association of lymph node status and the distribution pattern of ERα expression with tamoxifen responsiveness in this cohort of patients. In addition, a luminal-A-like patients with the heterogeneous ERα expression had a significantly shorter PFS time than those with the homogeneous ERα (P = 0.013). These results indicate that the heterogeneous expression of ERα is an accurate predictor of tamoxifen response and survival in luminal-A-like breast cancer patients. ESR1 rs2228480 may act as a marker with a high prognostic potential in luminal-B-like tumors.

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Acknowledgements

The study was supported by the Grant of the Russian Foundation for Basic Research No. 17‑29‑06037. 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, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 5 Kooperativny Street, Tomsk, Russian Federation, 634050

    Nataliya Babyshkina, Tatyana Dronova & Nadejda Cherdyntseva

  2. Department of General Oncology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation, 634050

    Elena Slonimskaya

  3. Department of Pathological Anatomy and Cytology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation, 634050

    Sergey Vtorushin

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

    Nataliya Babyshkina, Tatyana Dronova, Julia Kzhyshkowska & Nadejda Cherdyntseva

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

    Sergey Vtorushin, Elena Slonimskaya & Nadejda Cherdyntseva

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

    Julia Kzhyshkowska

  7. Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation, 634050

    Stanislav Patalyak & Evgeny Choynzonov

Authors
  1. Nataliya Babyshkina
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  2. Sergey Vtorushin
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  3. Tatyana Dronova
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  4. Stanislav Patalyak
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  5. Elena Slonimskaya
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  6. Julia Kzhyshkowska
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  7. Nadejda Cherdyntseva
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  8. Evgeny Choynzonov
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Correspondence to Nataliya Babyshkina.

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The authors declare that they have no conflict of interest.

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., Dronova, T. et al. Impact of estrogen receptor α on the tamoxifen response and prognosis in luminal-A-like and luminal-B-like breast cancer. Clin Exp Med 19, 547–556 (2019). https://doi.org/10.1007/s10238-019-00583-6

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  • DOI: https://doi.org/10.1007/s10238-019-00583-6

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