• 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, WECARE Study Collaborative Group, and Jonine L Bernstein.
• Memorial Sloan Kettering Cancer Center, New York, NY, USA.
• J. Natl. Cancer Inst. 2020 Dec 14; 112 (12): 1275-1279.

AbstractWhether 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.© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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