Open AccessRadiation Treatment, ATM, BRCA1/2, and CHEK2*1100delC Pathogenic Variants and Risk of Contralateral Breast Cancer
Author(s) -
Anne S. Reiner,
Mark E. Robson,
Lene Mellemkjær,
Marc Tischkowitz,
Esther M. John,
Charles F. Lynch,
Jennifer 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 A. Woodward,
Simon N. Powell,
David E. Goldgar,
Patrick Concan,
Jonine L. Bernstein
Publication year - 2020
Publication title -
journal of the national cancer institute
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.797
H-Index - 356
eISSN - 1460-2105
pISSN - 0027-8874
DOI - 10.1093/jnci/djaa031
Subject(s) - chek2 , breast cancer , medicine , oncology , missense mutation , penetrance , population , cancer , germline mutation , mutation , genetics , biology , gene , phenotype , environmental health
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.