Authors' objectives: The main objective of this evaluation was to summarise available evidence on the analytical validity, the clinical validity, and the clinical utility of molecular tests (Sanger sequencing, PCR, NGS, and Liquid chip technology), for the detection of PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha) mutations in men and postmenopausal women with hormone receptor positive (HR+)/human epidermal growth factor receptor2 negative (HER2–), locally advanced or metastatic breast cancer (BC) that has progressed during endocrine treatment.

Authors' results and conclusions: Results of this HTA is based on inadequate evidence on the accuracy of tests (various PCR assays and NGS-panels) for detection of PIK3CA mutations from three studies. Un-pooled results (5 tests and 3 comparisons) from single studies, with relatively small sample sizes, suggest good concordance between tests (Cohen’s ĸ: 0.80 to 0.86). All studies used plasma samples only. We did not identify any systematic reviews, or meta-analyses evaluating the accuracy of tests for the detection of PIK3CA mutations. None of the included studies reported on clinical utility. No evidence for the test accuracy of Sanger sequencing or Liquid chip methodologies were found. In our cost analysis, we included the costs for the tests of most relevance for a Norwegian context. Our results showed that for the detection of PIK3CA in isolation, the costs for testing using PCR is less than NGS-panel testing, however, using PCR for the detection of additional relevant mutations, will increase total cost. At present, the capital and infrastructure as well as maintenance costs are higher for NGS than the other diagnostic methods. Assuming that about 140 patients with metastatic BC annually are eligible for PIK3CA mutation testing annually, the costs were estimated to be ca NOK 322,000. The new reimbursement rates are insufficient to cover the costs of running PCR. The reimbursement rates for NGS testing can cover the costs of running the small NGS assays. In addition, new reimbursement rates have recently been defined for the expanded gene panels that mainly are used for the experimental treatment. All tests have both advantages and limitations, but due to incomplete information an adequate comparison was unfeasible. However, the choice of a suitable test for detecting PIK3CA mutations depends on accessibility of testing modalities, economic considerations, sample type and risk of false negatives, and the TAT. Future research should focus on conducting larger cohort studies with welldefined patient populations, that follows the patients from testing (or no testing), through treatment and final outcomes. Further, robust and replicable methods, as well as a reporting standard checklist, should be used for increased clarity.

Project Status: Completed

URL for project: https://www.fhi.no/en/publ/2022/Molecular-tests-for-detection-of-PIK3CA-mutations-in-men-and-postmenopausal-women-with-locally-advanced-metastatic-breast-cancer/

Year Published: 2022

URL for published report: https://www.fhi.no/en/publ/2022/Molecular-tests-for-detection-of-PIK3CA-mutations-in-men-and-postmenopausal-women-with-locally-advanced-metastatic-breast-cancer/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Norway

Organisation Name: Norwegian Institute of Public Health

Contact Address: P.O. Box 222 Skoyen, N-0123, Oslo