Does reproductive history impact breast cancer risk in BRCA carriers?

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Number and timing of pregnancies may affect breast cancer risk in BRCA mutation carriers, according to a new study, but the risks differ depending on whether the mutation is BRCA1 or BRCA2. The findings were published in JNCI Cancer Spectrum. 

The study assessed 9,232 women in a retrospective cohort and 3,886 in a prospective cohort. They were aged 18 to 80 years and had a known pathogenic BRCA1or BRCA2 mutation. The authors used weighted and time-varying Cox proportional hazards models to examine reproductive event in the two cohorts.

For BRCA1 carriers, the authors found that in women who had two, three, or four or more full-term pregnancies (FTP), breast cancer risk decreased by 21%, 30% and 50%, respectively. However, compared to being nulliparous, uniparous BRCA1 women were at an increased risk for breast cancer. The authors also found that increasing the duration of breastfeeding led to a reduction in breast cancer risk. Relative to a recent pregnancy, longer time since last full-term pregnancy (FTP) was associated with higher risk. 

For BRCA2 carriers, risk of breast cancer did not decrease with multiple pregnancies unless a woman had four or more FTPs (4 vs 1 HR = 0.72, 95% CI 0.54-0.98). Parous BRCA2 carriers with fewer than four FTPs had a 30% increase in breast cancer risk. That risk also increased as age at first FTP increased for this population. 

The authors believe that their findings can be helpful to ob/gyns when counseling their patients about family planning. The results can also be beneficial for refining breast cancer risk estimates and improving surveillance of mutation carriers based on their reproductive history.