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

Lisa Rydén (1) , Karin Jirström (2) , Monica Haglund (3) , Olle Stål (4) , Mårten Fernö (5)

1 Department of Surgery, Institution of Clinical Sciences
2 Center for Molecular Pathology, Department of Laboratory Medicine
3 Department of Clinical Pathology, Institution of Clinical Sciences
4 Department of Oncology, Clinical and Experimental Medicine, Faculty of Health Sciences [Linköping University ]
5 Department of Oncology, Institution of Clinical Sciences

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),  = 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.

Mots clés: Triple-negative breast cancer; Epidermal growth factor receptor; Gene copy number; Vascular endothelial growth factor receptor 2; Prognosis

Lisa Rydén, Karin Jirström, Monica Haglund, Olle Stål, Mårten Fernö. 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 Research and Treatment, 2010, 120 (2), pp.491-498. ⟨10.1007/s10549-010-0758-6⟩. ⟨hal-00535440⟩