Vascular endothelial growth factor receptor 2 is a significant negative prognostic biomarker in triple-negative breast cancer: results from a controlled randomised trial of premenopausal breast cancer.

Abstract

Abstract Abstract #1087 Background: Triple-negative breast cancer (TNB) is today an established phenotype of primary breast cancer recognized by estrogen (ER) negativity, progesterone (PgR) negativity and (human epidermal growth factor) HER2 negativity. The prognosis is poor and moreover patients with TNB dont benefit from established targeted drugs with antiestrogen therapies or trastuzumab. The role of other putative targets in TNB, like angiogenic markers and additional tyrosine kinase receptors is therefore a topic of interest in order to find effective targeted therapies improving the prognosis.
 Patients and methods: In a cohort of premenopausal breast cancer (n=564) randomized to adjuvant tamoxifen or no adjuvant treatment a tissue microarray was prepared from available primary tumors (n=500) and immunhistochemical (IHC) staining was performed including ER, PgR, HER2, vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor 2 (VEGFR2), epidermal receptor growth factor (EGFR) and platelet derived growth factor ß (PDGFR ß). HER2 status was additionally defined using fluorescence in situ hybridisation (FISH). Data regarding Nottingham histological grade (NHG) and Ki67, node status, tumour size and age was also included. All included patients were used for descriptive analysis, whereas only untreated patients were included in survival analysis.
 Results: In the whole cohort 96 patients had a TNB phenotype characterized by low age, high NGH (p<0.001), high Ki67-index (p<0.001), T2 tumors (p=0.002), N-negativity (p=0.004. EGFR-positivity (p<0.001) and tumor-specific VEGFR2 expression (p=0.03). TNB phenotype was not associated with VEGF-A or stromal expression of PDGFR ß, and was a significant prognostic factor for 10-year BCSS (HR 2.1 CI: 1.4-3.3) by univariate analysis in the untreated arm. The prognosis was further explored among TNB patients and VEGFR2 was a significant negative prognostic factor (HR 2.5 CI; 1.1-5.5) for 10-year BCSS, whereas VEGF-A , EGFR and PDGFR ß were not.
 Discussion: In a controlled randomized trial of premenopausal breastcancer, TNB was associated with worse prognosis. VEGFR2 was a significant prognostic biomarker for TNB patients which makes VEGFR2 a putative therapeutic target for this specific phenotype. Additional analysis of EGFR, VEGF-A and PDGFR ß did not add any prognostic information for TNB patients in this study. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1087.