Title

Management of Individuals with Heterozygous Germline Pathogenic Variants in ATM

Authoring Organization

Publication Month/Year

December 4, 2024

Last Updated Month/Year

December 10, 2024

Document Type

Consensus

Country of Publication

US

Document Objectives

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. An international workgroup developed a clinical practice resource to guide management of ATM heterozygotes using peer-reviewed publications and expert opinion. 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.

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Laboratory services

Intended Users

Genetics, nurse, nurse practitioner, physician, physician assistant

Scope

Counseling, Assessment and screening

Keywords

cancer predisposition, ATM, Cancer surveillance, cancer risk, Inherited cancer

Source Citation

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. Electronic address: documents@acmg.net. Management of individuals with heterozygous germline pathogenic variants in ATM: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2024 Dec 4:101243. doi: 10.1016/j.gim.2024.101243. Epub ahead of print. PMID: 39636577.