Until now, breasts were thought to grow only in the presence of the hormone estrogen. A combination of other factors before and during the period of breast development, including diet, obesity and metabolic syndrome — characterized by resistance to the hormone insulin — have also been correlated to a higher incidence of breast cancer later in life.
The striking new observations, published in the Proceedings of the National Academy of Sciences (PNAS), show that diet can initiate breast development in the absence of estrogen, and could magnify a genetic predisposition toward cancer.
Researchers found that if young mice were fed a diet high enough in a fatty acid, known as 10, 12 conjugated linoleic acid (10, 12 CLA), to induce symptoms similar to metabolic syndrome in humans, then mammary glands in the mice could grow even when estrogen had been eliminated either by removal of the ovaries or through estrogen-blocking drugs.
“This wasn’t supposed to happen,” said Russ Hovey, an associate professor at the UC Davis Animal Science Department and co-author of the study. “That has led us to step back, and almost challenge the textbooks, and say, ‘You know, [breast development] doesn’t, at the end of the day, unequivocally require estrogen.’ We’ve always assumed it does, but now this is telling us that it can happen through a separate pathway.”
A variety of mice strains, including one genetically predisposed to develop mammary tumors, were used in the experiments, have helped shed light on the relationship between diet, obesity and breast cancer risk, as well as the correlation between early breast development in girls and a growing epidemic of childhood obesity.
“We really look at this like it’s a model, where we can study it in a really controlled system,” said Grace Berryhill, a graduate student at the UC Davis Animal Science Department and lead author of the study. “We have a mouse, and we can feed it this diet, and create symptoms that would be in common with this particular metabolic syndrome in humans.”
Metabolic syndrome has become an increasingly hot topic of study in connection with a host of related health problems, including Type 2 diabetes and breast cancer. But teasing out the specific metabolic processes linking them has been difficult.
According to Hovey, the publishing of the PNAS paper is the first time it has been shown that something eaten can make the mammary glands grow.
“Now we are left with the question of whether anything that induces metabolic syndrome also gives the same effect, or if it is indeed more specific to a certain diet component,” Hovey said.
Colleen Sweeney, co-director of the breast cancer research program at the UC Davis Cancer Center, said the team’s work is a “high-impact study” that will change the way we think about breast cancer.
“I think their evidence really is astonishing,” Sweeney said. “It’s hard to argue with, because they have such beautiful in vivo data. The question is, what is the ultimate translation of these results? What could this mean for people potentially at risk for breast cancer?”
Hovey and his colleagues think that the answer probably starts with insulin resistance. In particular, that the dysregulation of insulin signaling brought on by the 10, 12 CLA-induced body changes could provide an important target for cancer therapies, an active area of current research. Future breakthroughs will depend on insights gained in both human and animal studies.
“Just because we’re animal scientists, doesn’t mean we milk cows all day,” Harvey joked. “So while this is mouse work, I suspect in the future this will be referred to, because it provides a potential explanation for the basis of why insulin might be an important target [for cancer therapy].”
OYANG TENG can be reached at firstname.lastname@example.org.