title: Breast cancer survival and tumor characteristics in premenopausal women carrying the CHEK2*1100delC germline mutation.
abstract: OBJECTIVE
  Women carrying a CHEK2*1100delC germline mutation have an increased risk of developing breast cancer. This study aims to determine the proportion of CHEK2*1100delC carriers in a premenopausal breast cancer population, unselected for family history of breast cancer, and to investigate tumor characteristics and disease outcome with sufficient follow-up.
  
  
  METHODS
  We identified a retrospective cohort of 1,479 patients, who received surgery for invasive breast cancer between 1970 and 1994. All patients were diagnosed before age 50. Paraffin-embedded tissue blocks were collected for DNA isolation (normal tissue), subsequent CHEK2*1100delC analysis, and tumor revision. Median follow-up was 10.1 years.
  
  
  RESULTS
  We detected a CHEK2*1100delC germline mutation in 54 patients (3.7%). Tumor characteristics of CHEK2*1100delC carriers did not differ significantly from those of noncarriers. CHEK2*1100delC carriers had a two-fold increased risk (hazard ratio [HR], 2.1; 95% CI, 1.0 to 4.3; P = .049) of developing a second breast cancer and they had worse recurrence-free survival (HR, 1.7; 95% CI, 1.2 to 2.4; P = .006) and worse breast cancer-specific survival (HR, 1.4; 95% CI, 1.0 to 2.1; P = .072) compared with noncarriers. The poorer disease outcome of CHEK2*1100delC carriers could not be explained by the increased risk of second breast cancer.
  
  
  CONCLUSIONS
  Our study, which is representative for the premenopausal breast cancer population, reveals approximately 4% CHEK2*1100delC carriers have an increased risk of second breast cancer and a worse long-term recurrence-free survival rate. Their identification at time of diagnosis and prolonged intensive follow-up should be considered to optimize clinical management.
authors.affiliation: Department of Epidemiology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Marjanka K
authors.initials: MK
authors.lastname: Schmidt
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: Sanne R
authors.initials: SR
authors.lastname: de Kemp
authors.forename: Annegien
authors.initials: A
authors.lastname: Broeks
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Cornelisse
authors.forename: Vincent T H B M
authors.initials: VT
authors.lastname: Smit
authors.forename: Johannes L
authors.initials: JL
authors.lastname: Peterse
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Van't Veer
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality*; D064447:Checkpoint Kinase 2; D018572:Disease-Free Survival; D005192:Family Health; D005260:Female; D005500:Follow-Up Studies; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017697:Premenopause; D016016:Proportional Hazards Models; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D012306:Risk; D016896:Treatment Outcome
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases