Abstract
PURPOSE: Germline CHEK2 c.1100delC-associated breast cancer (BC) patients have been reported with worse prognosis than patients without the variant. However, results are based on older cohorts and treatment regimens. As part of the Hebon-CHEK2 study, we aim to study prognosis in a Dutch cohort of genetically tested ER-positive BC patients diagnosed from 2006 onwards. METHODS: All patients underwent genetic testing based on personal and family history risk, and data on BC outcomes were collected. Hazard ratios (HRs) and 95 % confidence intervals (CI) for the association of CHEK2-status with prognosis were estimated via delayed entry Cox regression models, adjusted for age and year of diagnosis, tumor size, nodal status, and primary treatment regimens. Furthermore, we meta-analyzed our results with previous studies. RESULTS: We included 480 CHEK2 BC patients and 944 BC patients without the variant. Median follow-up was 6.0 years. Heterozygotes were more often diagnosed with small tumors, and lymph node positive disease. No significant difference was found for recurrent disease and distant disease-free survival, neither before 5 years (HR = 0.73; 95 %CI = 0.35-1.53 and HR = 0.99; 95 %CI = 0.44-2.21, respectively), nor after 5 years follow-up (HR = 0.29; 95 %CI = 0.06-1.28 and HR = 0.39; 95 %CI = 0.10-1.39, respectively). Also no significant difference in BC-specific survival (HR = 0.77; 95 %CI = 0.42-1.39) or overall survival (HR = 0.69; 95 %CI = 0.43-1.08) was found. Meta-analysis of our results with previous studies showed a worse BC-specific survival for heterozygotes. CONCLUSION: In our study, with more recent years of diagnosis and treatment, we found no difference in prognosis, as opposed to previous studies. Further research is needed to validate our findings.