Purpose: The role of CHEK2 in DNA repair by homologous recombination suggests that CHEK2-associated breast cancer (BC) patients might be more sensitive to chemotherapy inducing double-strand DNA breaks, but results hereon are lacking. We compared the sensitivity to first-line chemotherapy and endocrine therapy between CHEK2 1100delC and non-CHEK2 metastatic breast cancer (MBC) patients. Methods: Sixty-two CHEK2 1100delC MBC patients were selected from three cohorts genotyped for CHEK2 1100delC (one non-BRCA1/2 cohort and two sporadic cohorts). Controls were 62 non-CHEK2 MBC patients, matched for age at and year of primary BC diagnosis, and year of metastatic disease. Objective response rate (complete and partial response) to, and progression-free survival (PFS) and overall survival (OS) after start of first-line chemotherapy and endocrine therapy were compared between CHEK2 and non-CHEK2 patients. Results: Median age at BC diagnosis was 46 and 51 years at MBC diagnosis. First-line chemotherapy consisted of anthracycline-based chemotherapy (n = 73), taxanes (n = 16), CMF(-like) chemotherapy (n = 33) and taxane/anthracycline regimens (n = 2). CHEK2 and non-CHEK2 patients had a comparable objective response rate (44 vs. 52 %). Also, PFS and OS after start of chemotherapy were comparable between both patient groups (hazard ratio 0.91; 95 % confidence interval 0.63–1.30 and 1.03; 95 % CI 0.71–1.49, respectively). Thirty-six CHEK2 and 32 non-CHEK2 patients received first-line endocrine therapy (mainly tamoxifen) for MBC. No significant differences were observed in objective response rate to, and PFS and OS after start of endocrine therapy. Conclusion: No differential efficacy of chemotherapy and endocrine therapy given for MBC was observed in CHEK2 versus non-CHEK2 patients.

CHEK2 1100delC, Chemotherapy, Endocrine therapy, Metastatic breast cancer, Response, Survival
dx.doi.org/10.1007/s00432-015-1981-7, hdl.handle.net/1765/82651
Journal of Cancer Research and Clinical Oncology
Erasmus MC: University Medical Center Rotterdam

Kriege, M, Jager, A, Hollestelle, A, Berns, P.M.J.J, Blom, J, Meijer van Gelder, M.E, … Seynaeve, C.M. (2015). Sensitivity to systemic therapy for metastatic breast cancer in CHEK2 1100delC mutation carriers. Journal of Cancer Research and Clinical Oncology, 141(10), 1879–1887. doi:10.1007/s00432-015-1981-7