Effect of lifestyle and reproductive factors on the onset of breast cancer in female BRCA 1 and 2 mutation carriers.

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.,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.,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).,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.