title: The Lifetime Economic Burden of Inaccurate HER2 Testing: Estimating the Costs of False-Positive and False-Negative HER2 Test Results in US Patients with Early-Stage Breast Cancer.
abstract: BACKGROUND
  Patients with breast cancer whose tumors test positive for human epidermal growth factor receptor 2 (HER2) are treated with HER2-targeted therapies such as trastuzumab, but limitations with HER2 testing may lead to false-positive (FP) or false-negative (FN) results.
  
  
  OBJECTIVE
  To develop a US-level model to estimate the effect of tumor misclassification on health care costs and patient quality-adjusted life-years (QALYs).
  
  
  METHODS
  Decision analysis was used to estimate the number of patients with early-stage breast cancer (EBC) whose HER2 status was misclassified in 2012. FP results were assumed to generate unnecessary trastuzumab costs and unnecessary cases of trastuzumab-related cardiotoxicity. FN results were assumed to save money on trastuzumab, but with a loss of QALYs and greater risk of disease recurrence and its associated costs. QALYs were valued at $100,000 under a net monetary benefit approach.
  
  
  RESULTS
  Among 226,870 women diagnosed with EBC in 2012, 3.12% (n = 7,070) and 2.18% (n = 4,955) were estimated to have had FP and FN test results, respectively. Approximately 8400 QALYs (discounted, lifetime) were lost among women not receiving trastuzumab because of FN results. The estimated incremental per-patient lifetime burden of FP or FN results was $58,900 and $116,000, respectively. The implied incremental losses to society were $417 million and $575 million, respectively.
  
  
  CONCLUSIONS
  HER2 tests result in misclassification and nonoptimal treatment of approximately 12,025 US patients with EBC annually. The total economic societal loss of nearly $1 billion suggests that improvements in HER2 testing accuracy are needed and that further clinical and economic studies are warranted.
authors.affiliation: VeriTech Corporation, Mercer Island, WA, USA; University of Washington, Seattle, WA, USA. Electronic address: lgarrisn@u.washington.edu.
authors.forename: Louis P
authors.initials: LP
authors.lastname: Garrison
authors.affiliation: VeriTech Corporation, Mercer Island, WA, USA; University of Washington, Seattle, WA, USA.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Babigumira
authors.affiliation: Genentech, Inc., South San Francisco, CA, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Masaquel
authors.affiliation: Alliance Life Sciences, Somerset, NJ, USA.
authors.forename: Bruce C M
authors.initials: BC
authors.lastname: Wang
authors.affiliation: Genentech, Inc., South San Francisco, CA, USA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Lalla
authors.affiliation: Genentech, Inc., South San Francisco, CA, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Brammer
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis / Q000191:economics* / Q000235:genetics*; D017281:Cost of Illness; D003661:Decision Support Techniques; D042241:Early Diagnosis; D005188:False Negative Reactions; D005189:False Positive Reactions; D005260:Female; D005820:Genetic Testing / Q000191:economics* / Q000592:standards / Q000639:trends; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D014481:United States / Q000453:epidemiology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: HER2 testing; breast cancer; economic burden; trastuzumab