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Pregnancies tied to breast cancer odds for high-risk women

(Reuters Health) – Having more than one pregnancy has long been linked to lower odds of breast cancer, and a new study suggests that may hold true even for some women with genetic mutations that put them at high risk for these malignancies.

Researchers focused on women with mutations in two genes – BRCA1 and BRCA2 – that put them at a vastly increased risk of developing breast and ovarian tumors. Women with these gene mutations who do get cancer may have especially aggressive tumors that grow rapidly, spread quickly and are much harder to treat.

Compared to women with BRCA1 mutations who only had one full-term pregnancy, those who had two live births were 21 percent less likely to develop breast cancer, the study found. Having three pregnancies was tied to a 30 percent lower risk of breast cancer, and having four or more was associated with a 50 percent reduction in breast cancer risk.

However, one or more pregnancies increased the risk for women with BRCA2 mutations unless they had at least four.

“We see a different pattern of risk for BRCA1 and BRCA2 mutation carriers,” said lead study author Mary Beth Terry of the Columbia University Mailman School of Public Health in New York City.

Few studies to date have explored whether the number and timing of pregnancies influence breast cancer risk for women with BRCA1 and BRCA2 mutations, Terry’s team writes in the Journal of the National Cancer Institute.

With BRCA1 and BRCA2 mutations, roughly 70 percent of women will develop breast cancer by age 80, they note.

For the current study, researchers examined data on almost 8,000 women with BRCA1 mutations and more than 5,100 women with BRCA2 mutations.

Compared to those with no pregnancies, women with BRCA1 mutations who had only one full-term pregnancy were at an increased risk of breast cancer, as were women with BRCA2 mutations who had fewer than four pregnancies.

Longer duration of breastfeeding was associated with a lower risk of breast cancer for BRCA1 mutation carriers, the study also found.

With BRCA2 mutations, women had a greater risk of breast cancer when they were older at the time of their first pregnancy than when they started having kids earlier in life. Older first-time mothers with BRCA1 mutations didn’t appear to have a greater risk of breast cancer than their younger counterparts, however.

The study wasn’t designed to prove whether or how the number or timing of pregnancies might directly impact cancer risk. Researchers also lacked data on a variety of other factors that can influence cancer risk, and it’s possible that women who have multiple pregnancies might be healthier overall than women who have fewer kids.

Another limitation is that researchers didn’t look at whether women had what’s known as a preventive oophorectomy, or surgical removal of the ovaries, said Dr. Banu Arun, co-director of clinical cancer genetics at the University of Texas MD Anderson Cancer Center in Houston.

“Preventive oophorectomy after childbearing age is recommended in women with BRCA mutations, which was shown to potentially reduce breast cancer,” Arun, who wasn’t involved in the study, said by email. “It is possible that pregnancy related increased breast cancer risk could be offset with oophorectomy in BRCA2 mutation carriers.”

There also isn’t enough evidence yet to inform women’s choices about the number or timing of any pregnancies, said Dr. Richard Bleicher, a breast surgeon and professor of surgical oncology at Fox Chase Cancer Center in Philadelphia.

But the results do suggest pregnancy influences risk differently with BRCA1 and BRCA2 mutations.

“We often group BRCA1 and BRCA2 when we think about breast cancer, but these findings suggest differing risks and even disparate trends for each type of mutation carrier,” Bleicher, who wasn’t involved in the study, said by email. “If these findings are correct, it adds to our recognition that mutations in BRCA1 and BRCA2 do behave differently.”

SOURCE: Journal of the National Cancer Institute, online March 8, 2019.

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