Multiple Pregnancies Lower Risk of Breast Cancer in BRAC Mutation Carriers

Researchers in New York and Paris reported results of a large prospective study demonstrating that the lower risk extends to BRCA1 and BRCA2 mutation carriers.

It is well documented that there is a lower risk of breast cancer from multiple pregnancies and from breast feeding among women at average risk. The study included a retrospective cohort of 5,707 women with BRAC1 mutations and 3,535 women with BRAC2 mutations and a prospective cohort of 2,276 BRAC1 and 1,610 BRAC2 mutation carriers. Weighted and time-varying Cox proportional hazards models were used to assess whether reproductive events are associated with breast cancer risk for mutation carriers separately for each cohort and for the combined retrospective and prospective cohorts.

Among women with BRCA1 mutations, two, three, or four or more full-term pregnancies were associated with 21%, 30%, and 50% decreased risk in breast cancer compared with women with a single full-term pregnancy. Conversely, women with BRAC2 mutations had a decrease in risk only if they had four or more pregnancies. Women with BRCA1 mutations who had only one full-term pregnancy were at increased risk for breast cancer, as were women with BRCA2 mutations with fewer than four pregnancies.

“What we have learned is that timing really matters for many risk factors and the dual effect of pregnancy we see in non-mutation carriers with a long term protection but short term increase following pregnancy may not extend to all women with BRCA1 and BRCA2 mutations as the short-term increase and long-term protection may relate much more to the timing of when these pregnancies occur,” remarked lead author Mary Beth Terry, PhD, said of the study results.

Senior author Nadine Andrieu, PhD, added, “Moreover, the hormonal upheaval that occurs during the first pregnancy may have a more or less important impact on the risk of breast cancer depending on whether the first pregnancy occurs during periods of life at higher risk of developing a breast cancer or at less high risk, periods shifted by about ten years between BRAC2 and BRAC1 mutation carriers, with a later peak for BRAC2 mutation carriers.”

The study was published online in Journal of the National Cancer Institute Cancer Spectrum.