Detecting germline PTEN mutations among at-risk patients with cancer: An age- and sex-specific cost-effectiveness analysis

Joanne Ngeow, Chang Liu, Ke Zhou, Kevin Frick, David B. Matchar, Charis Eng

Research output: Contribution to journalArticle

Abstract

Purpose: 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. Patients and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)2537-2544
Number of pages8
JournalJournal of Clinical Oncology
Volume33
Issue number23
DOIs
StatePublished - Aug 10 2015

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Germ-Line Mutation
Cost-Benefit Analysis
Multiple Hamartoma Syndrome
Neoplasms
Costs and Cost Analysis
Mutation
Kidney Neoplasms
Early Detection of Cancer
Thyroid Gland
Breast

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Detecting germline PTEN mutations among at-risk patients with cancer : An age- and sex-specific cost-effectiveness analysis. / Ngeow, Joanne; Liu, Chang; Zhou, Ke; Frick, Kevin; Matchar, David B.; Eng, Charis.

In: Journal of Clinical Oncology, Vol. 33, No. 23, 10.08.2015, p. 2537-2544.

Research output: Contribution to journalArticle

Ngeow, Joanne ; Liu, Chang ; Zhou, Ke ; Frick, Kevin ; Matchar, David B. ; Eng, Charis. / Detecting germline PTEN mutations among at-risk patients with cancer : An age- and sex-specific cost-effectiveness analysis. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 23. pp. 2537-2544.
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