TY - JOUR
T1 - The most efficient and effective BRCA1/2 testing strategy in epithelial ovarian cancer
T2 - Tumor-First or Germline-First?
AU - Witjes, Vera M
AU - Ligtenberg, Marjolijn J L
AU - Vos, Janet R
AU - Braspenning, Jozé C C
AU - Ausems, Margreet G E M
AU - Mourits, Marian J E
AU - de Hullu, Joanne A
AU - Adang, Eddy M M
AU - Hoogerbrugge, Nicoline
N1 - Funding Information:
This work was supported by a grant from the Dutch Cancer Society ( KWF-KUN12732 ). The authors thank the Tumor-First project team for their help and support, particularly D.M.A Hermkens, Y.H.C.M. Smolders, and S. Dusseljee.
Publisher Copyright:
© 2023 The Authors
PY - 2023/7
Y1 - 2023/7
N2 - OBJECTIVE: Genetic testing in epithelial ovarian cancer (OC) is essential to identify a hereditary cause like a germline BRCA1/2 pathogenic variant (PV). An efficient strategy for genetic testing in OC is highly desired. We evaluated costs and effects of two strategies; (i) Tumor-First strategy, using a tumor DNA test as prescreen to germline testing, and (ii) Germline-First strategy, referring all patients to the clinical geneticist for germline testing.METHODS: Tumor-First and Germline-First were compared in two scenarios; using real-world uptake of testing and setting implementation to 100%. Decision analytic models were built to analyze genetic testing costs (including counseling) per OC patient and per family as well as BRCA1/2 detection probabilities. With a Markov model, the life years gained among female relatives with a germline BRCA1/2 PV was investigated.RESULTS: Focusing on real-world uptake, with the Tumor-First strategy more OC patients and relatives with a germline BRCA1/2 PV are detected (70% versus 49%), at lower genetic testing costs (€1898 versus €2502 per patient, and €2511 versus €2930 per family). Thereby, female relatives with a germline BRCA1/2 PV can live on average 0.54 life years longer with Tumor-First compared to Germline-First. Focusing on 100% uptake, the genetic testing costs per OC patient are substantially lower in the Tumor-First strategy (€2257 versus €4986).CONCLUSIONS: The Tumor-First strategy in OC patients is more effective in identifying germline BRCA1/2 PV at lower genetic testing costs per patient and per family. Optimal implementation of Tumor-First can further improve detection of heredity in OC patients.
AB - OBJECTIVE: Genetic testing in epithelial ovarian cancer (OC) is essential to identify a hereditary cause like a germline BRCA1/2 pathogenic variant (PV). An efficient strategy for genetic testing in OC is highly desired. We evaluated costs and effects of two strategies; (i) Tumor-First strategy, using a tumor DNA test as prescreen to germline testing, and (ii) Germline-First strategy, referring all patients to the clinical geneticist for germline testing.METHODS: Tumor-First and Germline-First were compared in two scenarios; using real-world uptake of testing and setting implementation to 100%. Decision analytic models were built to analyze genetic testing costs (including counseling) per OC patient and per family as well as BRCA1/2 detection probabilities. With a Markov model, the life years gained among female relatives with a germline BRCA1/2 PV was investigated.RESULTS: Focusing on real-world uptake, with the Tumor-First strategy more OC patients and relatives with a germline BRCA1/2 PV are detected (70% versus 49%), at lower genetic testing costs (€1898 versus €2502 per patient, and €2511 versus €2930 per family). Thereby, female relatives with a germline BRCA1/2 PV can live on average 0.54 life years longer with Tumor-First compared to Germline-First. Focusing on 100% uptake, the genetic testing costs per OC patient are substantially lower in the Tumor-First strategy (€2257 versus €4986).CONCLUSIONS: The Tumor-First strategy in OC patients is more effective in identifying germline BRCA1/2 PV at lower genetic testing costs per patient and per family. Optimal implementation of Tumor-First can further improve detection of heredity in OC patients.
KW - BRCA
KW - Cost analysis
KW - Genetic testing
KW - Heredity
KW - Ovarian cancer
UR - http://www.scopus.com/inward/record.url?scp=85159113259&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2023.04.029
DO - 10.1016/j.ygyno.2023.04.029
M3 - Article
C2 - 37182432
SN - 0090-8258
VL - 174
SP - 121
EP - 128
JO - Gynecologic Oncology
JF - Gynecologic Oncology
ER -