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Epidermal growth factor receptor and vascular endothelial growth factor receptor 2 are specific biomarkers in triple-negative breast cancer. Results from a controlled randomized trial with long-term follow-up

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Abstract

Triple-negative breast cancer (TNB) has poor prognosis and moreover patients with TNB do not benefit from established targeted drugs with endocrine therapy or trastuzumab. The aim of the study was to analyze the prevalence of candidate biomarkers in tumors from patients with TNB. Tissue microarrays were prepared from primary tumors from premenopausal breast cancer patients (500/564) randomized to adjuvant tamoxifen or no adjuvant treatment. Immunohistochemical (IHC) staining included ER, PR, HER2, epidermal receptor growth factor (EGFR), vascular endothelial growth factor A (VEGF-A), and vascular endothelial growth factor receptor 2 (VEGFR2). EGFR and HER2 gene copy number was defined by fluorescence in situ hybridization (FISH). All patients were included in the descriptive analysis, but only untreated patients in the survival analysis. TNB was diagnosed in 96 patients and correlated significantly to low age, Nottingham histological grade (NHG) III, high Ki67-index, T2 tumors, node negativity, EGFR positivity, increased EGFR gene copy number and high VEGFR2 expression. TNB was an independent prognostic factor for decreased 5-year breast cancer specific survival (BCSS) (HR 2.0 (95% CI 1.1–3.6), P = 0.01), but not for 10-year BCSS. High VEGFR2 expression was significantly correlated to decreased BCSS in TNB patients. TNB was associated with decreased BCSS and clinicopathological characteristics of an aggressive tumor type. High VEGFR2 expression, EGFR expression, and EGFR gene copy number were significantly correlated to TNB, supporting their role as putative candidate biomarkers for selection of targeted therapy in TNB.

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Acknowledgments

This study was supported by funds from the Gunnar, Arvid, and Elisabeth Nilsson Foundation; the Swedish Society for Medical Research; the Swedish Cancer Society; the Lund University Hospital Funds, Berta Kamprad Foundation; the Swedish Research Council; Governmental Funding of Clinical Research within the Nation Health Service and Skane county council’s research and development foundation.

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Authors and Affiliations

  1. Department of Surgery, Institution of Clinical Sciences, Lund University Hospital, SE 221 85, Lund, Sweden

    Lisa Rydén

  2. Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden

    Karin Jirström

  3. Department of Clinical Pathology, Institution of Clinical Sciences, Lund University, Lund, Sweden

    Monica Haglund

  4. Department of Oncology, Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden

    Olle Stål

  5. Department of Oncology, Institution of Clinical Sciences, Lund University, Lund, Sweden

    Mårten Fernö

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  1. Lisa Rydén
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  2. Karin Jirström
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  3. Monica Haglund
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  4. Olle Stål
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  5. Mårten Fernö
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Correspondence to Lisa Rydén.

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Rydén, L., Jirström, K., Haglund, M. et al. Epidermal growth factor receptor and vascular endothelial growth factor receptor 2 are specific biomarkers in triple-negative breast cancer. Results from a controlled randomized trial with long-term follow-up. Breast Cancer Res Treat 120, 491–498 (2010). https://doi.org/10.1007/s10549-010-0758-6

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  • DOI: https://doi.org/10.1007/s10549-010-0758-6

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