A common product of cholesterol may fuel breast tumor growth. Scientists have long struggled to understand why women with heart disease...
A common product of cholesterol may fuel breast tumor growth.
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.
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.
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