title: Immunohistochemical expression of HER2 in breast cancer: socioeconomic impact of inaccurate tests.
abstract: BACKGROUND
  Treatment for patients with breast cancer (BC) is guided by human epidermal growth factor receptor 2 (HER2) status. The patient's HER2 status is assessed using US Food and Drug Administration-approved in vitro diagnostic (IVD) immunohistochemical (IHC) tests and laboratory-developed IVD tests. We analysed HER2 testing accuracy using data from the Nordic Immunohistochemistry Quality Control (NordiQC) HER2 IHC programme; results were used in an economic BC treatment model.
  
  
  METHODS
  Data were obtained from NordiQC HER2 BC surveys performed from 2008 to 2012. False-negative (FN) and false-positive (FP) rates for approved and laboratory-developed IVDs were used to estimate direct costs, loss of survival, productivity benefit and quality-adjusted life-years. In the absence of consistent and accessible clinical and economic data from countries participating in the NordiQC programme, United States productivity data, healthcare costs and patient numbers were used as a surrogate in order to estimate the potential impact of selecting an approved or laboratory-developed IVDs.
  
  
  RESULTS
  In total, 1703 tests were performed. Pooled FN rates were 11% for approved IVDs and 25% for laboratory-developed IVDs; FP rates were 0% and 5%, respectively. Using these FP and FN rates in the economic model and applying them to the United States BC population, approved IVD tests would result in better clinical outcomes, i.e., better survival and fewer disease recurrences/progressions, and lower costs, i.e., total direct costs and lost productivity, versus laboratory-developed IVD tests. Every $1 saved by laboratories by using cheaper reagents could potentially result in approximately $6 additional costs to the healthcare system.
  
  
  CONCLUSIONS
  The results of this analysis suggest that incorrect HER2 test results have far-reaching clinical and economic consequences.
authors: NordiQC, Institute of Pathology, Aalborg University Hospital, Ladegaardsgade 3, DK-9000, Aalborg, Denmark. mv@rn.dk.
authors: Mogens
authors: M
authors: Vyberg
authors: NordiQC, Institute of Pathology, Aalborg University Hospital, Ladegaardsgade 3, DK-9000, Aalborg, Denmark. sn@rn.dk.
authors: Søren
authors: S
authors: Nielsen
authors: NordiQC, Institute of Pathology, Aalborg University Hospital, Ladegaardsgade 3, DK-9000, Aalborg, Denmark. rr@rn.dk.
authors: Rasmus
authors: R
authors: Røge
authors: Ventana Medical Systems Inc, 1910 E Innovation Park Drive, Tucson, AZ, 85755, USA. beth.sheppard@ventana.roche.com.
authors: Beth
authors: B
authors: Sheppard
authors: Ventana Medical Systems Inc, 1910 E Innovation Park Drive, Tucson, AZ, 85755, USA. jim.ranger-moore@ventana.roche.com.
authors: Jim
authors: J
authors: Ranger-Moore
authors: Ventana Medical Systems Inc, 1910 E Innovation Park Drive, Tucson, AZ, 85755, USA. eric.walk@ventana.roche.com.
authors: Eric
authors: E
authors: Walk
authors: F. Hoffmann-La Roche Ltd, Diagnostics Division, Divisional Medical and Scientific Affairs, CH-4070, Basel, Switzerland. juliane.gartemann@roche.com.
authors: Juliane
authors: J
authors: Gartemann
authors: F. Hoffmann-La Roche Ltd, Diagnostics Division, Divisional Medical and Scientific Affairs, CH-4070, Basel, Switzerland. ulrich-peter.rohr@roche.com.
authors: Ulrich-Peter
authors: UP
authors: Rohr
authors: F. Hoffmann-La Roche Ltd, Diagnostics Division, Divisional Medical and Scientific Affairs, CH-4070, Basel, Switzerland. volker.teichgraeber@roche.com.
authors: Volker
authors: V
authors: Teichgräber
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy*; D003951:Diagnostic Errors / Q000191:economics*; D005260:Female; D017048:Health Care Costs; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards*; D009364:Neoplasm Recurrence, Local; D019057:Quality-Adjusted Life Years; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012959:Socioeconomic Factors; D014481:United States
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human