Management of individuals with heterozygous germline pathogenic variants in ATM: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)
- Author(s)
- Pal, T; Schon, KR; Astiazaran-Symonds, E; Balmaña, J; Foulkes, WD; James, P; Klugman, S; Livinski, AA; Mak, JS; Ngeow, J; Voian, N; Wick, MJ; Hanson, H; Stewart, DR; Tischkowitz, M; ACMG Professional Practice and Guidelines Committee;
- Journal Title
- Genetics in Medicine
- Publication Type
- Online publication before print
- Abstract
- PURPOSE: ATM germline pathogenic variants (GPVs) are associated with a moderately increased risk of female breast cancer, pancreatic cancer, and prostate cancer. Resources for managing ATM heterozygotes in clinical practice are limited. METHODS: An international workgroup developed a clinical practice resource to guide management of ATM heterozygotes using peer-reviewed publications and expert opinion. RESULTS: Although ATM is a moderate (intermediate) penetrance gene, cancer risks may be considered as a continuous variable, influenced by family history and other modifiers. ATM GPV heterozygotes should generally be offered enhanced breast surveillance according to their personalized risk estimate and country-specific guidelines and, generally, risk-reducing mastectomy is not recommended. Prostate cancer surveillance should be considered. Pancreatic cancer surveillance should be considered based on assessment of family history, ideally as part of a clinical trial, with existence of country-specific guidelines. For ATM GPV heterozygotes who develop cancer, radiation therapy decisions should not be influenced by the genetic result. Although poly-adenosine diphosphate ribose polymerase inhibitors are licensed for use in metastatic castration-resistant prostate cancer and ATM GPVs, the evidence-base is currently weak. CONCLUSION: Systematic prospective data collection is needed to establish the spectrum of ATM-associated cancer and determine the outlines of surveillance, response to cancer treatment, and survival.
- Keywords
- Atm; Cancer predisposition; Cancer risk; Cancer surveillance; Inherited cancer
- Department(s)
- Familial Cancer Centre
- Publisher's Version
- https://doi.org/10.1016/j.gim.2024.101243
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-01-09 06:35:09
Last Modified: 2025-01-09 06:41:23