Radiation Treatment, ATM, BRCA1/2, and CHEK21100delC Pathogenic Variants and Risk of Contralateral Breast Cancer

Anne S Reiner; Mark E Robson; Lene Mellemkjær; Marc Tischkowitz; Esther M John; Charles F Lynch; Jennifer D Brooks; John D Boice; Julia A Knight; Sharon N Teraoka; Xiaolin Liang; Meghan Woods; Ronglai Shen; Roy E Shore; Daniel O Stram; Duncan C Thomas; Kathleen E Malone; Leslie Bernstein; Nadeem Riaz; Wendy Woodward; Simon Powell; David Goldgar; Patrick Concannon; Jonine L Bernstein; WECARE Study Collaborative Group

doi:10.1093/jnci/djaa031

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Radiation Treatment, ATM, BRCA1/2, and CHEK21100delC Pathogenic Variants and Risk of Contralateral Breast Cancer

Journal article

Open access

Peer reviewed

Radiation Treatment, ATM, BRCA1/2, and CHEK21100delC Pathogenic Variants and Risk of Contralateral Breast Cancer

Anne S Reiner, Mark E Robson, Lene Mellemkjær, Marc Tischkowitz, Esther M John, Charles F Lynch, Jennifer D Brooks, John D Boice, Julia A Knight, Sharon N Teraoka, …

JNCI : Journal of the National Cancer Institute, Vol.112(12), pp.1275-1279

12/14/2020

DOI: 10.1093/jnci/djaa031

PMCID: PMC7735763

PMID: 32119081

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735763View

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Abstract

Whether radiation therapy (RT) affects contralateral breast cancer (CBC) risk in women with pathogenic germline variants in moderate- to high-penetrance breast cancer-associated genes is unknown. In a population-based case-control study, we examined the association between RT; variants in ATM, BRCA1/2, or CHEK2*1100delC; and CBC risk. We analyzed 708 cases of women with CBC and 1399 controls with unilateral breast cancer, all diagnosed with first invasive breast cancer between 1985 and 2000 and aged younger than 55 years at diagnosis and screened for variants in breast cancer-associated genes. Rate ratios (RR) and 95% confidence intervals (CIs) were estimated using multivariable conditional logistic regression. RT did not modify the association between known pathogenic variants and CBC risk (eg, BRCA1/2 pathogenic variant carriers without RT: RR = 3.52, 95% CI = 1.76 to 7.01; BRCA1/2 pathogenic variant carriers with RT: RR = 4.46, 95% CI = 2.96 to 6.71), suggesting that modifying RT plans for young women with breast cancer is unwarranted. Rare ATM missense variants, not currently identified as pathogenic, were associated with increased risk of RT-associated CBC (carriers of ATM rare missense variants of uncertain significance without RT: RR = 0.38, 95% CI = 0.09 to 1.55; carriers of ATM rare missense variants of uncertain significance with RT: RR = 2.98, 95% CI = 1.31 to 6.80). Further mechanistic studies will aid clinical decision-making related to RT.

Adult

Ataxia Telangiectasia Mutated Proteins - genetics

BRCA1 Protein - genetics

BRCA2 Protein - genetics

Breast Neoplasms - genetics

Breast Neoplasms - pathology

Breast Neoplasms - radiotherapy

Case-Control Studies

Checkpoint Kinase 2 - genetics

Female

Genetic Predisposition to Disease

Germ-Line Mutation

Heterozygote

Humans

Middle Aged

Neoplasm Recurrence, Local - etiology

Neoplasm Recurrence, Local - genetics

Neoplasm Recurrence, Local - pathology

Neoplasms, Radiation-Induced - etiology

Neoplasms, Radiation-Induced - genetics

Neoplasms, Second Primary - etiology

Neoplasms, Second Primary - genetics

Penetrance

Radiotherapy - adverse effects

Sequence Deletion

Young Adult

Details

Title: Subtitle: Radiation Treatment, ATM, BRCA1/2, and CHEK21100delC Pathogenic Variants and Risk of Contralateral Breast Cancer
Creators: Anne S Reiner - Memorial Sloan Kettering Cancer Center, New York, NY, USA
Mark E Robson - Weill Cornell Medical College, Cornell University, New York, NY, USA
Lene Mellemkjær - Danish Cancer Society Research Center, Copenhagen, Denmark
Marc Tischkowitz - Department of Medical Genetics, University of Cambridge, Cambridge, UK
Esther M John - Stanford University, School of Medicine, Stanford, CA, USA
Charles F Lynch - University of Iowa, Iowa City, IA, USA
Jennifer D Brooks - University of Toronto, Dalla Lana School of Public Health Science, Toronto, ON, Canada
John D Boice - Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Bethesda, MD, USA
Julia A Knight - Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada
Sharon N Teraoka - Genetics Institute and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA
Xiaolin Liang - Memorial Sloan Kettering Cancer Center, New York, NY, USA
Meghan Woods - Memorial Sloan Kettering Cancer Center, New York, NY, USA
Ronglai Shen - Memorial Sloan Kettering Cancer Center, New York, NY, USA
Roy E Shore - NYU School of Medicine, New York, NY, USA
Daniel O Stram - University of Southern California, Los Angeles, CA, USA
Duncan C Thomas - University of Southern California, Los Angeles, CA, USA
Kathleen E Malone - Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Leslie Bernstein - Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
Nadeem Riaz - Memorial Sloan Kettering Cancer Center, New York, NY, USA
Wendy Woodward - MD Anderson Cancer Center, The University of Texas, Houston, TX, USA
Simon Powell - Memorial Sloan Kettering Cancer Center, New York, NY, USA
David Goldgar - University of Utah, School of Medicine, Salt Lake City, UT, USA
Patrick Concannon - Genetics Institute and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, USA
Jonine L Bernstein - Memorial Sloan Kettering Cancer Center, New York, NY, USA
WECARE Study Collaborative Group
Resource Type: Journal article
Publication Details: JNCI : Journal of the National Cancer Institute, Vol.112(12), pp.1275-1279
DOI: 10.1093/jnci/djaa031
PMID: 32119081
PMCID: PMC7735763
NLM abbreviation: J Natl Cancer Inst
ISSN: 0027-8874
eISSN: 1460-2105
Publisher: Oxford University Press
Grant note: R01 CA206464 / NCI NIH HHS P30 CA016672 / NCI NIH HHS R01 ES027121 / NIEHS NIH HHS
Language: English
Date published: 12/14/2020
Academic Unit: Epidemiology
Record Identifier: 9984214716802771

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