New research shows that women who have larger babies have more than twice the risk of breast cancer, compared with mothers who give birth to smaller infants.What’s the connection? In a study published in the journal PLoS ONE, scientists led by Dr. Radek Bukowski, a professor of obstetrics and gynecology at the University of Texas Medical Branch, suggest that having a heavier baby may create a hormonal environment in pregnancy that encourages the future development of breast cancer. The findings fall in line with previous studies linking babies’ birth weight to mothers’ breast cancer risk later in life, but the current study sought to separate that association from other breast cancer risk factors, such as the mother’s own weight. Heavier mothers tend to have heavier babies as well.For the study, Bukowski and his colleagues followed 410 women who gave birth to their first child while participating in the Framingham Offspring Birth History Study. The women were tracked between 1991 and 2008, and researchers collected data on the birth weight of the women’s first baby, as well as on other breast cancer risk factors, including the age at which they had their first period, their age at menopause, race, body mass index (BMI) and whether they used hormone replacement therapy.During the 17 years of follow-up, 31 women were diagnosed with breast cancer. Women who had had the largest babies — born in the top fifth of weight — were 2.5 times more likely to develop breast cancer than women whose babies were born in the lowest weight categoryEven after Bukowski’s team adjusted for other potentially confounding breast cancer risk factors, including women’s weight, family history, use of hormones and number of subsequent pregnancies, the relationship between larger first babies and cancer remained. "We found that large babies are independent of traditional risk factors for breast cancer,” says Bukowski. "In essence, they have a different mechanism for triggering cancer.”To shed more light on that potential mechanism, the researchers looked 23,824 women participating in another study called the First and Second Trimester Evaluation of Risk for Aneuploidy, or FASTER. These women, who had given birth to singleton babies between 1999 and 2003, also provided blood samples to measure levels of several breast-cancer-related hormones that soar during pregnancy: estriol, a weak form of estrogen made by the placenta of pregnant women; alphafetoprotein (AFP), an anti-estrogen; and a hormone known as PAPP-A that increases concentrations of insulin-like growth factor in the blood, which is associated with breast cancer.Women who delivered the biggest babies — 8.25 lbs. or larger — were found to have what the researchers called a "pro-carcinogenic environment,” with high levels of estrogen, low levels of anti-estrogen and the presence of free insulin-like growth factors. Women whose babies were in the top quintile of weight were 25% more likely than women with smaller babies to have the highest ratios of estriol to AFP, and therefore more estrogen circulating in their bodies; these women were also 25% more likely to have the highest levels of PAPP-A. "It looks like during pregnancy, when a woman carries a big baby, the hormonal milieu favors breast cancer development,” says Bukowski. "And we also showed a possible mechanism for why that might happen.”• The researchers note, for example, that animal studies have suggested that breast stem cells, which are involved in breast cancer development, may increase or decrease in number in response to hormone exposure, including during pregnancy. These cells may "retain a memory of prior hormone exposure,” the authors write, which could help explain the increase in breast cancer risk in women following pregnancy with large babies. In other words, the pregnancy hormones may create a long-term effect that could lead to breast cancer later.• The hormonal shifts associated with large babies appear to have exceptionally powerful effects. Previous studies have found that women’s risk of breast cancer goes down if they have more than one child; the assumption has been that exposure to progesterone, another reproductive hormone that soars by an order of magnitude during pregnancy, can counter the cancer-promoting effects of estrogen. Having a large baby, however, may interfere with this normal mix of hormones and favor a condition in which estrogen is more dominant. Even women in the current study who went on to have more children experienced a higher risk of breast cancer if their first baby was larger, compared with women whose first babies were smaller. "We know that regardless of how many children a woman had, her first child’s birth weight was significant for breast cancer risk,” says Bukowski.While it’s still premature to suggest using birth weight as a predictor of women’s breast-cancer risk, Bukowski hopes that the current findings will spur more research on that possibility — and on the relationship between hormonal environments during pregnancy and cancer. Since data on babies’ birth weight is easily obtainable (and most mothers probably remember it), it could be an easy way to screen women at risk, or at least serve as another reason for women to try to lower their cancer risk by getting regular exercise, eating better, improving health overall and participating in regular screening.• Especially because there may be decades of lag time between birth and potential development of cancer — on average, the time between the birth of the first child to breast cancer diagnosis was about 38 years in Bukowski’s study, and the median age at diagnosis was 61 — it gives women plenty of time modify certain health risk factors. Adopted from Time magazine