TY - JOUR
T1 - Management of individuals with heterozygous germline pathogenic variants in ATM
T2 - A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)
AU - Pal, Tuya
AU - Schon, Katherine R.
AU - Astiazaran-Symonds, Esteban
AU - Balmaña, Judith
AU - Foulkes, William D.
AU - James, Paul
AU - Klugman, Susan
AU - Livinski, Alicia A.
AU - Mak, Julie S.
AU - Ngeow, Joanne
AU - Voian, Nicoleta
AU - Wick, Myra J.
AU - Hanson, Helen
AU - Stewart, Douglas R.
AU - Tischkowitz, Marc
N1 - Publisher Copyright:
© 2024 American College of Medical Genetics and Genomics
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - ATM
KW - Cancer predisposition
KW - Cancer risk
KW - Cancer surveillance
KW - Inherited cancer
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U2 - 10.1016/j.gim.2024.101243
DO - 10.1016/j.gim.2024.101243
M3 - Article
AN - SCOPUS:85211014138
SN - 1098-3600
JO - Genetics in Medicine
JF - Genetics in Medicine
M1 - 101243
ER -