title: Effect of lifestyle and reproductive factors on the onset of breast cancer in female BRCA 1 and 2 mutation carriers.
abstract: BACKGROUND
  The birth year-dependent onset of breast cancer (BC) in BRCA1/2 mutation carriers suggests a risk-modifying role for reproductive and life style factors. We therefore examined possible associations between these factors and age at diagnosis.
  
  
  METHODS
  Cox regression analysis and log-Rank testing were used to estimate the effect of potential life style factors on the onset of BC in 197 BRCA mutation carriers.
  
  
  RESULTS
  Nulliparous BRCA mutation carriers developed BC earlier than those who had delivered (36.4 vs. 40.9; P = 0.001). Similarly, smokers and women who had used oral contraceptives experienced an earlier cancer onset (39.0 vs. 41.4; P = 0.05 and 39.3 vs. 44.9; P = 0.0001, respectively). In multivariate analysis, oral contraceptive use (HR: 1.7; P = 0.006) and birth cohort (< vs. ≥1965 HR: 4.5; P = 0.001) were associated with an earlier BC onset, while previous pregnancies led to a delay (HR: 0.2; P = 0.04). Mutation carriers born ≥1965 were less likely to have experienced pregnancies and more likely to have used oral contraceptives, and consequently developed BC at an earlier age (median age: 42 vs. 58; P < 0.0001 log-Rank test).
  
  
  CONCLUSIONS
  We here demonstrate that in BRCA1/2 mutation carriers the birth cohort-associated differences in the onset of BC are profound and influenced by reproductive factors.
authors.affiliation: Department of OB/GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Rieder
authors.affiliation: Department of Thoracic Surgery Otto Wagner Hospital Vienna Austria.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Salama
authors.affiliation: Department of OB/GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria.
authors.forename: Lena
authors.initials: L
authors.lastname: Glöckner
authors.affiliation: Department of OB/GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Muhr
authors.affiliation: Department of OB/GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Berger
authors.affiliation: Department of OB/GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria.
authors.forename: Muy-Kheng
authors.initials: MK
authors.lastname: Tea
authors.affiliation: Department of OB/GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Pfeiler
authors.affiliation: Department of OB/GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Rappaport-Fuerhauser
authors.affiliation: Department of OB/GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria.
authors.forename: Daphne
authors.initials: D
authors.lastname: Gschwantler-Kaulich
authors.affiliation: Department of OB/GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Weingartshofer
authors.affiliation: Department of OB/GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
keywords: BRCA mutation; breast cancer onset; lifestyle factors; reproductive factors