Purpose: To describe a snapshot of international genetic testing practices, specifically regarding the use of multigene panels, for hereditary breast/ovarian cancers. We conducted a survey through the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium, covering questions about 16 non-BRCA1/2 genes.
Methods: Data were collected via in-person and paper/electronic surveys. ENIGMA members from around the world were invited to participate. Additional information was collected via country networks in the United Kingdom and in Italy.
Results: Responses from 61 cancer genetics practices across 20 countries showed that 16 genes were tested by > 50% of the centers, but only six (PALB2, TP53, PTEN, CHEK2, ATM, and BRIP1) were tested regularly. US centers tested the genes most often, whereas United Kingdom and Italian centers with no direct ENIGMA affiliation at the time of the survey were the least likely to regularly test them. Most centers tested the 16 genes through multigene panels; some centers tested TP53, PTEN, and other cancer syndrome-associated genes individually. Most centers reported (likely) pathogenic variants to patients and would test family members for such variants. Gene-specific guidelines for breast and ovarian cancer risk management were limited and differed among countries, especially with regard to starting age and type of imaging and risk-reducing surgery recommendations.
Conclusion: Currently, a small number of genes beyond BRCA1/2 are routinely analyzed worldwide, and management guidelines are limited and largely based on expert opinion. To attain clinical implementation of multigene panel testing through evidence-based management practices, it is paramount that clinicians (and patients) participate in international initiatives that share panel testing data, interpret sequence variants, and collect prospective data to underpin risk estimates and evaluate the outcome of risk intervention strategies.
Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings.J Cancer Res Clin Oncol. 2018 Dec;144(12):2495-2513. doi: 10.1007/s00432-018-2763-9. Epub 2018 Oct 10. J Cancer Res Clin Oncol. 2018. PMID: 30306255
Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment.JAMA Oncol. 2015 Oct;1(7):943-51. doi: 10.1001/jamaoncol.2015.2690. JAMA Oncol. 2015. PMID: 26270727 Clinical Trial.
ENIGMA--evidence-based network for the interpretation of germline mutant alleles: an international initiative to evaluate risk and clinical significance associated with sequence variation in BRCA1 and BRCA2 genes.Hum Mutat. 2012 Jan;33(1):2-7. doi: 10.1002/humu.21628. Epub 2011 Nov 3. Hum Mutat. 2012. PMID: 21990146 Free PMC article.
Time to incorporate germline multigene panel testing into breast and ovarian cancer patient care.Breast Cancer Res Treat. 2016 Dec;160(3):393-410. doi: 10.1007/s10549-016-4003-9. Epub 2016 Oct 12. Breast Cancer Res Treat. 2016. PMID: 27734215 Review.
Genetic Tests for Breast and Ovarian Cancer [Internet].Oslo, Norway: Knowledge Centre for the Health Services at The Norwegian Institute of Public Health (NIPH); 2008 Feb. Report from Norwegian Knowledge Centre for the Health Services (NOKC) No. 05-2008. Knowledge Centre for the Health Services at The Norwegian Institute of Public Health (NIPH). 2008. PMID: 29319983 Free Books & Documents. Review.
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Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers.J Exp Clin Cancer Res. 2020 Mar 4;39(1):46. doi: 10.1186/s13046-020-01554-6. J Exp Clin Cancer Res. 2020. PMID: 32127026 Free PMC article. Review.
Genetic Predisposition to Breast and Ovarian Cancers: How Many and Which Genes to Test?Int J Mol Sci. 2020 Feb 8;21(3):1128. doi: 10.3390/ijms21031128. Int J Mol Sci. 2020. PMID: 32046255 Free PMC article. Review.