The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Abstract

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.