Scientists have long struggled to understand why women with heart disease risk factors are more likely to develop breast cancer. Now research suggests that high cholesterol may play an important role.
Estrogen drives the majority of breast cancers in women. The hormone binds to proteins known as receptors inside the tumor, helping it grow. So when Philip Shaul, a pediatrician and biologist at the University of Texas Southwestern Medical Center, and his colleagues learned that a common breakdown product of cholesterol also activates estrogen receptors, they thought they might be on to something. Teaming up with Duke University cancer biologist Donald McDonnell, they showed in 2008 that the cholesterol product, known as 27HC, spurs tumor growth in human breast cancer cells.
Building on their work, Shaul and McDonnell showed, in independent studies published in November 2013 in Cell Reports and Science, respectively, that 27HC drives cancer growth in mice harboring estrogen receptor–positive human breast tumors. Using samples from patients at his hospital, Shaul also found that 27HC levels were three times higher in the healthy breast tissue of women with breast cancer compared with that of cancer-free women; 27HC levels were 2.3 times higher still in tumor cells. Furthermore, cancer patients who had lower levels of an enzyme that breaks down 27HC in tumors were less likely to survive. When McDonnell's team fed mice high-cholesterol or high-fat diets, they were more likely than animals with normal diets to develop breast cancer, too. The two papers “bring 27HC to the ‘limelight’ of breast cancer research,” says Sérgio Dias, a biologist at the Institute of Molecular Medicine in Lisbon.
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It is still unclear, however, how blood cholesterol levels might affect breast cancer risk because Shaul found no consistent link between 27HC levels in human tumors and blood cholesterol levels. “But there may be subsets of women with high cholesterol at greater risk,” he says.
The findings could have important treatment implications. They bolster the idea, backed already by one study, that cholesterol-lowering statin drugs may slow the progression of some breast cancers. And because between 30 and 65 percent of women with estrogen-fueled breast cancers do not respond to drugs that thwart estrogen production, the studies suggest that in some women “there's simply an entirely different driver of the cancer,” Shaul says.