title: Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy.
abstract: BACKGROUND
  We assessed the sensitivity to adjuvant chemotherapy in cell cycle checkpoint kinase 2 (CHEK2) vs non-CHEK2 breast cancer patients by comparing the contralateral breast cancer incidence and distant disease-free and breast cancer-specific survival between both groups, stratified for adjuvant chemotherapy.
  
  
  METHODS
  One Dutch hereditary non-BRCA1/2 breast cancer patient cohort (n=1220) and two Dutch cohorts unselected for family history (n=1014 and n=2488, respectively) were genotyped for CHEK2 1100delC. Hazard ratios for contralateral breast cancer, distant disease-free and breast cancer-specific death for mutation carriers vs noncarriers were calculated using the Cox proportional hazard method, stratified for adjuvant chemotherapy.
  
  
  RESULTS
  The CHEK2 mutation carriers (n=193) had an increased incidence of contralateral breast cancer (multivariate hazard ratio 3.97, 95% confidence interval 2.59-6.07). Distant disease-free and breast cancer-specific survival were similar in the first 6 years in mutation carriers compared with noncarriers, but diverted as of 6 years after breast cancer diagnosis (multivariate hazard ratios and 95% confidence intervals 2.65 (1.79-3.93) and 2.05 (1.41-2.99), respectively). No significant interaction between CHEK2 and adjuvant chemotherapy was observed.
  
  
  CONCLUSIONS
  The CHEK2 1100delC-associated breast cancer is associated with a higher contralateral breast cancer rate as well as worse survival measures beyond 6 years after diagnosis. No differential sensitivity to adjuvant chemotherapy was observed in CHEK2 patients.
authors.affiliation: Family Cancer Clinic, Department of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Kriege
authors.affiliation: Family Cancer Clinic, Department of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Hollestelle
authors.affiliation: Family Cancer Clinic, Department of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Jager
authors.affiliation: Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: P E A
authors.initials: PE
authors.lastname: Huijts
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Centre Cancer Institute, Rotterdam, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: Berns
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Centre Cancer Institute, Rotterdam, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Sieuwerts
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Centre Cancer Institute, Rotterdam, The Netherlands.
authors.forename: M E
authors.initials: ME
authors.lastname: Meijer-van Gelder
authors.affiliation: Family Cancer Clinic, Department of Clinical Genetics, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Collée
authors.affiliation: Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Devilee
authors.affiliation: Family Cancer Clinic, Department of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Hooning
authors.affiliation: Family Cancer Clinic, Department of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
authors.forename: J W M
authors.initials: JW
authors.lastname: Martens
authors.affiliation: Family Cancer Clinic, Department of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Seynaeve
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D064447:Checkpoint Kinase 2 / Q000235:genetics*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D009154:Mutation / Q000235:genetics
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human