Unrecognised actionability for breast cancer risk variants identified in a national-level review of Australian familial cancer centres

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dc.contributor.authorFortuno, C.
dc.contributor.authorCops, E.J.
dc.contributor.authorDavidson, A.L.
dc.contributor.authorHadler, J.
dc.contributor.authorInnella, G.
dc.contributor.authorMcKenzie, M.E.
dc.contributor.authorParsons, M.
dc.contributor.authorCampbell, A.M.
dc.contributor.authorDubowsky, A.
dc.contributor.authorFargas, V.
dc.contributor.authorField, M.J.
dc.contributor.authorMar Fan, H.G.
dc.contributor.authorNichols, C.B.
dc.contributor.authorPoplawski, N.K.
dc.contributor.authorWarwick, L.
dc.contributor.authorWilliams, R.
dc.contributor.authorBeshay, V.
dc.contributor.authorEdwards, C.
dc.contributor.authorJohns, A.
dc.contributor.authorMcPhillips, M.
dc.contributor.authoret al.
dc.date.issued2024
dc.description.abstractBreast cancer remains a significant global health challenge. In Australia, the adoption of publicly-funded multigene panel testing for eligible cancer patients has increased accessibility to personalised care, yet has also highlighted the increasing prevalence of variants of uncertain significance (VUS), complicating clinical decision-making. This project aimed to explore the spectrum and actionability of breast cancer VUS in Australian familial cancer centers (FCCs). Leveraging data from 11 FCCs participating in the Inherited Cancer Connect database, we retrieved VUS results from 1472 patients. Through ClinVar crosschecks and application of gene-specific ACMG/AMP guidelines, we showed the potential for reclassification of 4% of unique VUS as pathogenic or likely pathogenic, and 80% as benign or likely benign. Surveys conducted with FCCs and diagnostic laboratories described current practices and challenges in variant reclassifications, highlighting resource constraints preventing periodic VUS review and notifications from the laboratories to the FCCs. Our study suggests there are benefits to routine VUS review and reclassification, particularly in publicly-funded healthcare systems. Future research should focus on assessing the clinical impact and cost-effectiveness of implementing routine variant review practices, alongside efforts to enhance communication between FCCs and laboratories.
dc.description.statementofresponsibilityCristina Fortuno, Elisa J. Cops, Aimee L. Davidson, Johanna Hadler, Giovanni Innella, Maddison E. McKenzie, Michael Parsons, Ainsley M. Campbell, Andrew Dubowsky, Verna Fargas, Michael J. Field, Helen G. Mar Fan, Cassandra B. Nichols, Nicola K. Poplawski, Linda Warwick, Rachel Williams, Victoria Beshay, Caitlin Edwards, Andrea Johns, Mary McPhillips, Vanessa Siva Kumar, Rodney Scott, Mark Williams, Hamish Scott, Paul A. James and Amanda B. Spurdle
dc.identifier.citationEuropean Journal of Human Genetics, 2024; 32(12):1632-1639
dc.identifier.doi10.1038/s41431-024-01705-9
dc.identifier.issn1018-4813
dc.identifier.issn1476-5438
dc.identifier.orcidPoplawski, N.K. [0000-0002-9372-3325]
dc.identifier.orcidScott, H. [0000-0002-5813-631X]
dc.identifier.urihttps://hdl.handle.net/2440/143839
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/177524
dc.rights© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.source.urihttp://dx.doi.org/10.1038/s41431-024-01705-9
dc.subjectGenetic testing
dc.subject.meshHumans
dc.subject.meshBreast Neoplasms
dc.subject.meshGenetic Predisposition to Disease
dc.subject.meshAustralia
dc.subject.meshFemale
dc.subject.meshGenetic Testing
dc.titleUnrecognised actionability for breast cancer risk variants identified in a national-level review of Australian familial cancer centres
dc.typeJournal article
pubs.publication-statusPublished

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