The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations
BACKGROUND: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following a FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. METHODS: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5,707 BRCA1 and 3,525 BRCA2 mutation carriers) and a prospective cohort (2,276 BRCA1 and 1,610 BRCA2 mutation carriers), separately for each cohort and in the combined, prospective and retrospective, cohort. RESULTS: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (Combined Hazard Ratio (HRc)=0.99, 95%CI=0.83-1.18). Relative to being uniparous, increased number of FTPs was associated with decreased BC risk (HRc=0.79, 95%CI=0.69-0.91; HRc=0.70, 95%CI=0.59-0.82; HRc=0.50, 95%CI=0.40-0.63, for 2, 3, and ≥4 FTPs, respectively, ptrend<0.0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort ptrend=0.0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective cohort (HRp=1.69, 95%CI=1.09-2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc=1.33, 95%CI=1.05-1.69) and there was no apparent decrease in risk associated with multiparity except for ≥4 FTPs (HRc=0.72, 95%CI=0.54-0.98). CONCLUSIONS: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.
Cancer Research UK (20861)
Cancer Research UK (A16563)
Cancer Research UK (A17523)