title: Sensitivity to systemic therapy for metastatic breast cancer in CHEK2 1100delC mutation carriers.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  No differential efficacy of chemotherapy and endocrine therapy given for MBC was observed in CHEK2 versus non-CHEK2 patients.
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands, a.kriege@erasmusmc.nl.
authors.forename: Mieke
authors.initials: M
authors.lastname: Kriege
authors.forename: Agnes
authors.initials: A
authors.lastname: Jager
authors.forename: Antoinette
authors.initials: A
authors.lastname: Hollestelle
authors.forename: Els M J J
authors.initials: EM
authors.lastname: Berns
authors.forename: Jannet
authors.initials: J
authors.lastname: Blom
authors.forename: Marion E
authors.initials: ME
authors.lastname: Meijer-van Gelder
authors.forename: Anieta M
authors.initials: AM
authors.lastname: Sieuwerts
authors.forename: Ans
authors.initials: A
authors.lastname: van den Ouweland
authors.forename: J Margriet
authors.initials: JM
authors.lastname: Collée
authors.forename: Judith R
authors.initials: JR
authors.lastname: Kroep
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
authors.forename: Maartje J
authors.initials: MJ
authors.lastname: Hooning
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D064447:Checkpoint Kinase 2 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D043823:Taxoids / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D043823:Taxoids; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human