title: Therapeutic targeting of integrin αvβ6 in breast cancer.
abstract: BACKGROUND
  Integrin αvβ6 promotes migration, invasion, and survival of cancer cells; however, the relevance and role of αvβ6 has yet to be elucidated in breast cancer.
  
  
  METHODS
  Protein expression of integrin subunit beta6 (β6) was measured in breast cancers by immunohistochemistry (n > 2000) and ITGB6 mRNA expression measured in the Molecular Taxonomy of Breast Cancer International Consortium dataset. Overall survival was assessed using Kaplan Meier curves, and bioinformatics statistical analyses were performed (Cox proportional hazards model, Wald test, and Chi-square test of association). Using antibody (264RAD) blockade and siRNA knockdown of β6 in breast cell lines, the role of αvβ6 in Human Epidermal Growth Factor Receptor 2 (HER2) biology (expression, proliferation, invasion, growth in vivo) was assessed by flow cytometry, MTT, Transwell invasion, proximity ligation assay, and xenografts (n ≥ 3), respectively. A student's t-test was used for two variables; three-plus variables used one-way analysis of variance with Bonferroni's Multiple Comparison Test. Xenograft growth was analyzed using linear mixed model analysis, followed by Wald testing and survival, analyzed using the Log-Rank test. All statistical tests were two sided.
  
  
  RESULTS
  High expression of either the mRNA or protein for the integrin subunit β6 was associated with very poor survival (HR = 1.60, 95% CI = 1.19 to 2.15, P = .002) and increased metastases to distant sites. Co-expression of β6 and HER2 was associated with worse prognosis (HR = 1.97, 95% CI = 1.16 to 3.35, P = .01). Monotherapy with 264RAD or trastuzumab slowed growth of MCF-7/HER2-18 and BT-474 xenografts similarly (P < .001), but combining 264RAD with trastuzumab effectively stopped tumor growth, even in trastuzumab-resistant MCF-7/HER2-18 xenografts.
  
  
  CONCLUSIONS
  Targeting αvβ6 with 264RAD alone or in combination with trastuzumab may provide a novel therapy for treating high-risk and trastuzumab-resistant breast cancer patients.
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Kate M
authors: KM
authors: Moore
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Gareth J
authors: GJ
authors: Thomas
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Stephen W
authors: SW
authors: Duffy
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Jane
authors: J
authors: Warwick
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Rhian
authors: R
authors: Gabe
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Patrick
authors: P
authors: Chou
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Ian O
authors: IO
authors: Ellis
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Andrew R
authors: AR
authors: Green
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Syed
authors: S
authors: Haider
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Kellie
authors: K
authors: Brouilette
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Antonio
authors: A
authors: Saha
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Sabari
authors: S
authors: Vallath
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Rebecca
authors: R
authors: Bowen
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Claude
authors: C
authors: Chelala
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Diana
authors: D
authors: Eccles
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: William J
authors: WJ
authors: Tapper
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Alastair M
authors: AM
authors: Thompson
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Phillip
authors: P
authors: Quinlan
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Lee
authors: L
authors: Jordan
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Cheryl
authors: C
authors: Gillett
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Adam
authors: A
authors: Brentnall
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Shelia
authors: S
authors: Violette
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Paul H
authors: PH
authors: Weinreb
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Jane
authors: J
authors: Kendrew
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Simon T
authors: ST
authors: Barry
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: Ian R
authors: IR
authors: Hart
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB).
authors: J Louise
authors: JL
authors: Jones
authors: Affiliations of authors: Centre for Tumour Biology (KMM, GJT, KB, AS, SV, RB, IRH, JLJ, JFM), Cancer Screening Evaluation Group (SWD, JW, RG, PC), and Molecular Oncology and Imaging (SH, CC), John Vane Science Centre, Barts Cancer Institute, Queen Mary University of London, London, UK; Department of Histopathology, Molecular Medical Sciences, Nottingham City Hospital NHS Trust, Nottingham, UK (IOE, ARG); Cancer Sciences Division, Southampton General Hospital, Southampton, UK (GJT, DE, WJT); Department of Surgery (AMT, PQ) and Department of Pathology (LJ), Ninewells Hospital and Medical School, Dundee, UK; Hedley Atkins Breast Pathology Laboratory, Guy's Hospital, London, UK (CG); Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventative Medicine, Queen Mary University of London, London, UK (AB); Biogen Idec, Cambridge, MA (SV, PHW); Oncology iMED, AstraZeneca, Macclesfield, UK (JK, STB). j.f.marshall@qmul.ac.uk.
authors: John F
authors: JF
authors: Marshall
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D051379:Mice; D016513:Mice, SCID; D058990:Molecular Targeted Therapy / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D000068878:Trastuzumab; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D016023:Integrins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C073878:integrin alphavbeta6; C508053:ERBB2 protein, human