title: Detecting Germline PTEN Mutations Among At-Risk Patients With Cancer: An Age- and Sex-Specific Cost-Effectiveness Analysis.
abstract: OBJECTIVE
  Cowden syndrome (CS) is an autosomal dominant disorder characterized by benign and malignant tumors. One-quarter of patients who are diagnosed with CS have pathogenic germline PTEN mutations, which increase the risk of the development of breast, thyroid, uterine, renal, and other cancers. PTEN testing and regular, intensive cancer surveillance allow for early detection and treatment of these cancers for mutation-positive patients and their relatives. Individual CS-related features, however, occur commonly in the general population, making it challenging for clinicians to identify CS-like patients to offer PTEN testing.
  
  
  METHODS
  We calculated the cost per mutation detected and analyzed the cost-effectiveness of performing selected PTEN testing among CS-like patients using a semi-quantitative score (the PTEN Cleveland Clinic [CC] score) compared with existing diagnostic criteria. In our model, first-degree relatives of the patients with detected PTEN mutations are offered PTEN testing. All individuals with detected PTEN mutations are offered cancer surveillance.
  
  
  RESULTS
  CC score at a threshold of 15 (CC15) costs from $3,720 to $4,573 to detect one PTEN mutation, which is the most inexpensive among the different strategies. At base-case, CC10 is the most cost-effective strategy for female patients who are younger than 40 years, and CC15 is the most cost-effective strategy for female patients who are between 40 and 60 years of age and male patients of all ages. In sensitivity analyses, CC15 is robustly the most cost-effective strategy for probands who are younger than 60 years.
  
  
  CONCLUSIONS
  Use of the CC score as a clinical risk calculator is a cost-effective prescreening method to identify CS-like patients for PTEN germline testing.
authors.affiliation: Joanne Ngeow, Charis Eng, Cleveland Clinic; Charis Eng, Case Western Reserve University and School of Medicine, Cleveland, Ohio; Joanne Ngeow, National Cancer Centre; Joanne Ngeow, Chang Liu, Ke Zhou, David B. Matchar, Duke-NUS Graduate Medical School, Singapore; and Kevin D. Frick, The Johns Hopkins Carey Business School, Baltimore, MD.
authors.forename: Joanne
authors.initials: J
authors.lastname: Ngeow
authors.affiliation: Joanne Ngeow, Charis Eng, Cleveland Clinic; Charis Eng, Case Western Reserve University and School of Medicine, Cleveland, Ohio; Joanne Ngeow, National Cancer Centre; Joanne Ngeow, Chang Liu, Ke Zhou, David B. Matchar, Duke-NUS Graduate Medical School, Singapore; and Kevin D. Frick, The Johns Hopkins Carey Business School, Baltimore, MD.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Joanne Ngeow, Charis Eng, Cleveland Clinic; Charis Eng, Case Western Reserve University and School of Medicine, Cleveland, Ohio; Joanne Ngeow, National Cancer Centre; Joanne Ngeow, Chang Liu, Ke Zhou, David B. Matchar, Duke-NUS Graduate Medical School, Singapore; and Kevin D. Frick, The Johns Hopkins Carey Business School, Baltimore, MD.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Joanne Ngeow, Charis Eng, Cleveland Clinic; Charis Eng, Case Western Reserve University and School of Medicine, Cleveland, Ohio; Joanne Ngeow, National Cancer Centre; Joanne Ngeow, Chang Liu, Ke Zhou, David B. Matchar, Duke-NUS Graduate Medical School, Singapore; and Kevin D. Frick, The Johns Hopkins Carey Business School, Baltimore, MD.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Frick
authors.affiliation: Joanne Ngeow, Charis Eng, Cleveland Clinic; Charis Eng, Case Western Reserve University and School of Medicine, Cleveland, Ohio; Joanne Ngeow, National Cancer Centre; Joanne Ngeow, Chang Liu, Ke Zhou, David B. Matchar, Duke-NUS Graduate Medical School, Singapore; and Kevin D. Frick, The Johns Hopkins Carey Business School, Baltimore, MD.
authors.forename: David B
authors.initials: DB
authors.lastname: Matchar
authors.affiliation: Joanne Ngeow, Charis Eng, Cleveland Clinic; Charis Eng, Case Western Reserve University and School of Medicine, Cleveland, Ohio; Joanne Ngeow, National Cancer Centre; Joanne Ngeow, Chang Liu, Ke Zhou, David B. Matchar, Duke-NUS Graduate Medical School, Singapore; and Kevin D. Frick, The Johns Hopkins Carey Business School, Baltimore, MD engc@ccf.org.
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
mesh_terms: D000328:Adult; D000368:Aged; D003362:Cost-Benefit Analysis; D055088:Early Detection of Cancer; D005260:Female; D005820:Genetic Testing / Q000191:economics*; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011159:Population Surveillance; D014481:United States
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human