Journal of the National Cancer Institute
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J. Natl. Cancer Inst. · Dec 2020
Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women.
The risks of breast cancer in African American (AA) women associated with inherited mutations in breast cancer predisposition genes are not well defined. Thus, whether multigene germline hereditary cancer testing panels are applicable to this population is unknown. We assessed associations between mutations in panel-based genes and breast cancer risk in 5054 AA women with breast cancer and 4993 unaffected AA women drawn from 10 epidemiologic studies. ⋯ The study identifies genes that predispose to breast cancer in the AA population, demonstrates the validity of current breast cancer testing panels for use in AA women, and provides a basis for increased referral of AA patients for cancer genetic testing.
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J. Natl. Cancer Inst. · Dec 2020
Radiation Treatment, ATM, BRCA1/2, and CHEK2*1100delC Pathogenic Variants and Risk of Contralateral Breast Cancer.
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. ⋯ 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.