Radiation treatment, ATM, BRCA1/2, and CHEK2*1100delC pathogenic variants, and risk of contralateral breast cancer
Menée à partir de données sur la période 1985-2000 portant sur 708 patientes atteintes d'un cancer du sein controlatéral et sur 1 399 témoins atteintes d'un cancer du sein unilatéral (âge : 55 ans au diagnostic), cette étude analyse l'effet de la radiothérapie sur le risque de cancer du sein associé à des mutations pathogènes connues (ATM, BRCA 1/2, CHEK2*1100delC)
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 1,399 controls with unilateral breast cancer, all diagnosed with first invasive breast cancer between 1985-2000, <55 years of age at diagnosis, and screened for variants in breast cancer-associated genes. Rate ratios and 95% confidence intervals were estimated using multivariable conditional logistic regression. RT did not modify the association between known pathogenic variants and CBC risk (e.g., BRCA1/2 pathogenic variant carriers without RT, RR: 3.52, 95% CI: 1.76-7.01; BRCA1/2 pathogenic variant carriers with RT, RR: 4.46, 95% CI: 2.96-6.71), 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: 0.09-1.55; carriers of ATM rare missense variants of uncertain significance with RT, RR: 2.98, 95% CI: 1.31-6.80). Further mechanistic studies will aid clinical decision-making related to RT.