title: Upregulation of IGF-1R expression during neoadjuvant therapy predicts poor outcome in breast cancer patients.
abstract: BACKGROUND
  The insulin-like growth factor 1 receptor (IGF-1R) may be involved in the development of resistance against conventional cancer treatment. The aim of this study was to assess whether IGF-1R expression of breast tumors changes during neoadjuvant therapy and to study whether these changes were associated with survival.
  
  
  METHODS
  Paraffin embedded tumor tissue was collected from pretreatment biopsies and surgical resections of 62 breast cancer patients who were treated with neoadjuvant chemotherapy or endocrine therapy. IGF-1R expression was determined immunohistochemically and compared before and after treatment.
  
  
  RESULTS
  High membranous IGF-1R expression at diagnosis correlated significantly with ER positivity, low tumor stage (stage I/II) and longer overall survival (p < 0.05). After neoadjuvant treatment, membranous IGF-1R expression remained the same in 41 (65%) tumors, was upregulated in 11 (18%) tumors and downregulated in 11 (18%) tumors. Changes in membranous IGF-1R expression were associated with overall survival (log-rank test: p = 0.013, multivariate cox-regression: p = 0.086). Mean overall survival time for upregulation, no change, and downregulation in IGF-1R expression was 3.0 ± 0.5 years, 7.3 ± 1.0 years and 15.0 ± 1.8 years, respectively. Changes in other parameters were not significantly associated with survival.
  
  
  CONCLUSIONS
  Neoadjuvant therapy can induce changes in IGF-1R expression. Upregulation of IGF-1R expression after neoadjuvant treatment is a poor prognostic factor in breast cancer patients, providing a rationale for incorporating anti-IGF-1R drugs in the management of these patients.
authors: Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Sandra
authors: S
authors: Heskamp
authors: Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Otto C
authors: OC
authors: Boerman
authors: Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Janneke D M
authors: JD
authors: Molkenboer-Kuenen
authors: Department of Pathology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
authors: Carla A
authors: CA
authors: Wauters
authors: Department of Surgery, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
authors: Luc J A
authors: LJ
authors: Strobbe
authors: Department of Internal Medicine, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
authors: Caroline M P W
authors: CM
authors: Mandigers
authors: Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors: Peter
authors: P
authors: Bult
authors: Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Wim J G
authors: WJ
authors: Oyen
authors: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Winette T A
authors: WT
authors: van der Graaf
authors: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors: Hanneke W M
authors: HW
authors: van Laarhoven
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D017526:Receptor, IGF Type 1