Skip to main content

Breast Cancer Risk in BRCA1/2 Mutation Carriers Modified by Pregnancies, Breastfeeding

NEW YORK (GenomeWeb) – Cancer-related mutations in the BRCA1 and BRCA2 genes seem to show distinct breast cancer risk profiles in relation to pregnancy, new research suggests.

Members of a large, international team retrospectively and prospectively considered breast cancer risk in the context of reproductive history for thousands of women carrying risky BRCA1 or BRCA2 mutations. Their findings, published in the Journal of the National Cancer Institute Cancer Spectrum journal online last week, hinted that giving birth to a single child was associated with increased breast cancer risk in BRCA1 mutation carriers, for example, while BRCA2 mutation carriers had an uptick in breast cancer after giving birth at least once.

"These findings might help refine the [breast cancer] risk estimates and make it possible to adapt the surveillance of mutation carriers according to their reproductive life history," corresponding author Nadine Andrieu, a cancer genetic epidemiology researcher at the Curie Institute, and her colleagues wrote.

Prior studies have suggested that overall breast cancer risk declines in the long term in women who have gone through full-term pregnancy, the team noted, despite an uptick in breast cancer cases diagnosed shortly after full-term pregnancy. With that in mind, the researchers set out to understand the relationship between breast cancer, BRCA1/2 mutations, and women's birth histories in prospective and retrospective analyses.

"Given the earlier age at which [breast cancer] risk increases for women carrying a BRCA1 or BRCA2 mutation, it is important to know whether the [breast cancer risk] for carriers is modified by the number and timing of their pregnancies and/or by breast-feeding," the authors explained. "However, the few studies that assessed associations with pregnancies and breast-feeding for BRCA1/2 mutation carriers have reported inconsistent results."

The researchers prospectively followed 3,886 BRCA1 or BRCA2 mutation carriers, along with 9,232 mutation carriers considered retrospectively, comparing breast cancer risk according to BRCA1/2 mutation carriage and reproductive history. The participants were classified as "nulliparous" (women who have not given birth), "uniparous" (women who have given birth to one child), and "multiparous" (women who have given birth to multiple children).

On the BRCA2 mutation side, the researchers' retrospective analysis pointed to a drop in breast cancer risk for women who gave birth to multiple children, though that pattern was not reproduced in the prospective analysis. They noted that breast cancer risk in the BRCA2 mutation carriers edged up alongside women's age at first full-term pregnancy. And parity — a history of child birth — seemed to coincide with an uptick in breast cancer cases compared with nulliparity, or no history of child birth, in the BRCA2 mutation carriers.

On the other hand, the team's retrospective analysis hinted that distinct age-related patterns might impact women with BRCA1 mutations. There, BRCA1 mutations were associated with a slight decline in breast cancer risk with increasing age at first full-term pregnancy. Likewise, in the retrospective arm of the study, breast cancer risk associated with cancer-related BRCA1 mutations appeared to decline somewhat for women who breast-fed their children for longer stretches of time.

In the prospective cohort, the researchers found that BRCA1 mutation carriers who gave birth to one child tended to have higher rates of breast cancer compared to women with BRCA1 mutations who had given birth to no children or to more than one child. Even so, they reported that overall breast cancer risk did not show significant ties to women's birthing history: the combined analysis saw no association between parity or nulliparity and breast cancer in the women with BRCA1 mutations.

"These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers," the authors wrote.