Abstract
Overexpression of EGFR, HER2 and HER3 are known to be associated with poor outcome in breast cancer. Few studies have examined the clinical impact of activation of these proteins. In the present study, we evaluated EGFR, HER2 and HER3 and the activated (phosphorylated) forms of these proteins in patients with early breast cancer. EGFR, HER2, HER3, pEGFR, pHER2 and pHER3 expression was determined by immunohistochemical analysis of tissue microarrays constructed from tumours within the Edinburgh Breast Conservation Series (BCS). The BCS represents a fully-documented consecutive cohort of 1,812 patients treated by breast conservation surgery in a single institution. Our results demonstrate overexpression of HER2 and pHER2 to be associated with a significant reduction in overall survival (OS) (HR: 1.66, 95 % CI 1.22-2.26, p = 0.001 and HR: 1.57, 95 % CI 1.22-2.03, p = 0.001, respectively) and distant relapse-free survival (DRFS) (HR: 1.63, 95 % CI 1.23-2.18, p = 0.001 and HR: 1.55, 95 % CI 1.23-1.97, p = 0.0002, respectively). Paradoxically, expression of pEGFR was associated with a significantly improved OS (HR: 0.67 95 % CI 0.50-0.91, p = 0.01) and DRFS (HR: 0.73, 95 % CI 0.56-0.96, p = 0.025). Expression of activated EGFR/HER2 p...Continue Reading
References
Jan 9, 1987·Science·D J SlamonW L McGuire
Jan 1, 1994·Molecular and Cellular Biology·P FediM H Kraus
Jan 5, 1996·The Journal of Biological Chemistry·S P Soltoff, L C Cantley
Dec 1, 1998·Stem Cells·J S Ross, J A Fletcher
Apr 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·L N KlapperY Yarden
Jan 29, 2000·Molecular and Cellular Biology·G A RodriguesJ Schlessinger
Nov 1, 2000·Cell·J Schlessinger
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·Y Yarden, M X Sliwkowski
Oct 13, 2001·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Y Yarden
Jul 8, 2003·The Journal of Pathology·Caroline J WittonJohn M S Bartlett
Jul 31, 2003·British Journal of Cancer·J EdwardsJ M S Bartlett
Oct 14, 2004·British Journal of Cancer·D M Abd El-RehimI O Ellis
Oct 19, 2004·Seminars in Oncology·Yosef YardenDavid Miles
Feb 3, 2005·The Journal of Pathology·John M S BartlettJoanne Edwards
Feb 19, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael P DiGiovannaAnn D Thor
Jul 8, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sian ToveyJohn M S Bartlett
Jul 27, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Lisa M McShaneUNKNOWN Statistics Subcommittee of the NCI-EORTC Working Group on Cancer Diagnostics
Aug 10, 2005·The Journal of Pathology·Tove KirkegaardJohn M S Bartlett
Aug 18, 2005·British Journal of Cancer·L M McShaneUNKNOWN Statistics Subcommittee of the NCI-EORTC Working Group on Cancer Diagnostics
Sep 29, 2005·PLoS Medicine·Heidi GreulichMatthew Meyerson
Nov 8, 2005·Nature·Richard B JonesGavin MacBeath
Apr 12, 2006·Breast Cancer Research : BCR·Sian M ToveyJohn M S Bartlett
May 26, 2006·Histopathology·T KirkegaardJ M S Bartlett
Aug 17, 2006·Cancer Research·Kendall D CareyMark X Sliwkowski
Aug 26, 2006·Breast Cancer Research and Treatment·Lisa M McShaneUNKNOWN Statistics Subcommittee of NCI-EORTC Working Group on Cancer Diagnostics
Sep 28, 2006·Breast Cancer Research and Treatment·Elizabeth CanningsJohn M S Bartlett
Aug 1, 2007·BMC Genomics·Katherine A HoadleyCharles M Perou
Oct 2, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Yago NietoSamia Nawaz
Oct 2, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·John M S BartlettPaul Ellis
Mar 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Maggie C U CheangTorsten O Nielsen
Apr 3, 2008·Journal of Clinical Pathology·R A WalkerS E Pinder
Jun 5, 2008·Breast Cancer Research : BCR·Christina MagkouIoanna Giannopoulou
Sep 5, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·John M S BartlettChris J Twelves
Oct 29, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Brian R Leyland-JonesUNKNOWN Children's Oncology Group
Feb 26, 2009·Breast Cancer Research : BCR·Thomas FrogneAnne E Lykkesfeldt
Oct 23, 2009·Histopathology·Jeremy St J ThomasJohn M S Bartlett
Mar 11, 2011·Breast Cancer Research and Treatment·Melanie SpearsJohn M S Bartlett