Arnoud J Templeton1, Laura Diez-Gonzalez2, Olga Ace1, Francisco Vera-Badillo1, Boštjan Seruga3, Joaquín Jordán2, Eitan Amir1, Atanasio Pandiella4, Alberto Ocaña5. 1. Divisions of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Department of Medicine, University of Toronto, Toronto, Canada. 2. Translational Oncology Unit, Albacete University Hospital, Albacete, Spain. 3. Department of Medical Oncology, Institute of Oncology Ljubljana, Slovenia. 4. IBMCC-CSIC, Universidad de Salamanca, Spain. 5. Translational Oncology Unit, Albacete University Hospital, Albacete, Spain. Electronic address: albertoo@sescam.jccm.es.
Abstract
BACKGROUND: Receptor tyrosine kinases (RTKs) may facilitate tumor progression if activated aberrantly. The prognostic impact of human epidermal growth factor receptor 2 (HER2) overexpression and effectiveness of its therapeutic targeting is well established, but the effects on prognosis of overexpression of other RTKs is unknown. Here we evaluate the association of RTK expression and survival in breast cancer. METHODS: PubMed was searched to identify studies evaluating the association between expression of RTKs other than HER2 and survival of women with breast cancer. Published data were extracted and computed into odds ratios (OR) for death at 5 years with 95% confidence intervals (CI). Data were pooled in a meta-analysis using the Mantel-Haenszel random-effect model. For studies reporting data for more than one RTK the lowest and highest OR were used for separate analyses. RESULTS: Sixteen studies comprising 11,056 patients were included in the analysis. There was an association between overexpression of RTKs and decreased 5-year OS and this was highly significant when using highest ORs from studies reporting more than one RTK (OR=2.42; 95% CI=1.92-3.06, P<0.001). Similar results were observed for 5-year BCSS. Worse OS was seen with overexpression of fibroblast growth factor receptor 2/3 (FGFR) (OR=3.81; 95% CI=1.79-8.11) and epidermal growth factor receptor (EGFR)/HER1 (OR=2.45; 95% CI=1.90-3.15). CONCLUSION: Overexpression of various RTKs is associated with poor outcomes. This data suggests the clinical evaluation of combination of agents against RTKs or relevant oncogenic nodes.
BACKGROUND: Receptor tyrosine kinases (RTKs) may facilitate tumor progression if activated aberrantly. The prognostic impact of human epidermal growth factor receptor 2 (HER2) overexpression and effectiveness of its therapeutic targeting is well established, but the effects on prognosis of overexpression of other RTKs is unknown. Here we evaluate the association of RTK expression and survival in breast cancer. METHODS: PubMed was searched to identify studies evaluating the association between expression of RTKs other than HER2 and survival of women with breast cancer. Published data were extracted and computed into odds ratios (OR) for death at 5 years with 95% confidence intervals (CI). Data were pooled in a meta-analysis using the Mantel-Haenszel random-effect model. For studies reporting data for more than one RTK the lowest and highest OR were used for separate analyses. RESULTS: Sixteen studies comprising 11,056 patients were included in the analysis. There was an association between overexpression of RTKs and decreased 5-year OS and this was highly significant when using highest ORs from studies reporting more than one RTK (OR=2.42; 95% CI=1.92-3.06, P<0.001). Similar results were observed for 5-year BCSS. Worse OS was seen with overexpression of fibroblast growth factor receptor 2/3 (FGFR) (OR=3.81; 95% CI=1.79-8.11) and epidermal growth factor receptor (EGFR)/HER1 (OR=2.45; 95% CI=1.90-3.15). CONCLUSION: Overexpression of various RTKs is associated with poor outcomes. This data suggests the clinical evaluation of combination of agents against RTKs or relevant oncogenic nodes.
Authors: Nadia B Hassounah; Martha Nunez; Colleen Fordyce; Denise Roe; Ray Nagle; Thomas Bunch; Kimberly M McDermott Journal: Mol Cancer Res Date: 2017-06-13 Impact factor: 5.852
Authors: Antonino Musolino; Mario Campone; Patrick Neven; Neelima Denduluri; Carlos H Barrios; Javier Cortes; Kimberly Blackwell; Hatem Soliman; Zsuzsanna Kahan; Hervé Bonnefoi; Matthew Squires; Yong Zhang; Stephanie Deudon; Michael M Shi; Fabrice André Journal: Breast Cancer Res Date: 2017-02-10 Impact factor: 6.466