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- Title
Radiation Treatment, ATM, BRCA1/2, and CHEK2*1100delC Pathogenic Variants and Risk of Contralateral Breast Cancer.
- Authors
Reiner, Anne S; Robson, Mark E; Mellemkjær, Lene; Tischkowitz, Marc; John, Esther M; Lynch, Charles F; Brooks, Jennifer D; Boice, John D; Knight, Julia A; Teraoka, Sharon N; Liang, Xiaolin; Woods, Meghan; Shen, Ronglai; Shore, Roy E; Stram, Daniel O; Thomas, Duncan C; Malone, Kathleen E; Bernstein, Leslie; Riaz, Nadeem; Woodward, Wendy
- 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.
- Subjects
BREAST cancer; AUTOMATED teller machines; RADIATION carcinogenesis; YOUNG women; PROTEINS; PROTEIN kinases; GENETIC mutation; CANCER relapse; CASE-control method; GENETIC carriers; SECONDARY primary cancer; DISEASE susceptibility; RADIOTHERAPY; BREAST tumors; PHENOTYPES
- Publication
JNCI: Journal of the National Cancer Institute, 2020, Vol 112, Issue 12, p1275
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djaa031