Bilateral Disease Common Among Slovenian CHEK2-Positive Breast Cancer Patients

Background Currently, data on pathogenic variants in theCHEK2gene and their impact on cancer risk are lacking. This study aimed to explore the characteristics of breast cancer (BC) patients from families withCHEK2pathogenic variants in Slovenia. Methods In the years 2014 to 2019,CHEK2pathogenic variants/likely pathogenic variants (PV/LPVs) were found in probands from 50 different families who underwent genetic counseling and testing using a multigene panel at the authors' institution. Altogether, the study enrolled 75 individuals from 50CHEK2families who were carriers of aCHEK2PV/LPV. The clinical data on 41 BC patients withCHEK2PV/LPV and other carriers ofCHEK2PV/LPV from Slovenia were collected and analyzed. Results Breast cancer was diagnosed in 41 of 75CHEK2PV/LPV carriers (40 females, 1 male). The mean age at BC diagnosis was 42.8 years (range, 21-63 years), and 27 (65.8%) of the 41 of patients with BC had a positive family history for BC. Contralateral BC (CBC) was observed in 8 (19.5%) of the 41 patients (mean age, 55.6 years). Of 12 patients with human epidermal growth factor receptor 2 (HER2)-positive tumor type, a c.444+1G > A PV/LPV was detected in 4 patients, c.349A > G in 3 patients, deletion of exons 9-10 in 3 patients, deletion of exon 8 in 1 patient, and c.1427C > T PV/LPV in 1 patient. Conclusion Bilateral BC was diagnosed in as many as 19.5% of the Slovenian BC patients withCHEK2PV/LPVs. Breast cancer associated with a germlineCHEK2PV/LPV occurs in younger patients compared with sporadic BC.