People who are at risk for developing breast cancer, especially
those who are genetically predisposed, should take special care to
cut fat and cholesterol out of their diets.
New research Kimmel Cancer Center at Thomas Jefferson
University shows elevated fat and cholesterol levels found in a
typical American-style diet play an important role in the growth
and spread of breast cancer,
The study, published in the January issue of The American Journal
of Pathology, examines the role of fat and cholesterol in breast
cancer development using the PyMT mouse model, which is believed to
closely parallel the pathogenesis of human breast cancer.
The results show that mice fed a Western diet, and predisposed to
develop mammary tumors, can develop larger tumors that are faster
growing and metastasize more easily, compared to animals eating a
control diet.
The incidence rate of breast cancer is five times higher in Western countries than in other developed countries.
Moreover, studies have shown an increase in breast cancer incidence in immigrant populations that relocate from a region with low incidence.
"These facts suggest strong environmental influence on breast cancer development," said Frank.
Dietary fat and cholesterol have been shown to be important risk factors in the development and progression of a number of tumor types, but diet-based studies in humans have reached contradictory conclusions.
This has led Frank to turn to animal models of human cancer to examine links between cholesterol, diet, and cancer.
Some of the PyMT mice were placed on a diet that contained 21.2 percent fat and 0.2 percent cholesterol, reflective of a typical Western diet. A control group of PyMT mice was fed a normal chow that had only 4.5 percent fat and negligible amounts of cholesterol.
The researchers found tumors began to develop quickly in mice fed the fat/cholesterol-enriched chow.
In this group, the number of tumors was almost doubled, and they
were 50 percent larger than those observed in mice that ate a
normal diet.
"The consumption of a Western diet resulted in accelerated tumor
onset and increased tumor incidences, multiplicity, and burden,
suggesting an important role for dietary cholesterol in tumor
formation," said Frank.
There was also a trend towards an increased number of lung
metastasis in mice fed the fatty diet, he adds.
To confirm the aggressive nature of the cancer in animals fed a
cholesterol-rich diet, the researchers examined the levels of
several biomarkers of tumor progression and found a signature of a
more advanced cancer stage, compared to tumors that developed in
the control group.
The researchers also showed plasma cholesterol levels in
experimental mice that developed tumors were significantly reduced
compared to a group of "wild-type" mice -- animals with no
predisposition to develop tumors -- that was also fed a
cholesterol-rich diet.
"This suggests that tumor formation was responsible for the
reduction in blood cholesterol levels observed in our animals,"
said Frank.
Cholesterol, basically, helps tumors grow and spread.
"In a neighborhood, if you want to build more houses, you need
more bricks. In tumors, cholesterol provides the bricks that are
the foundation for further growth, and this cholesterol comes from
the blood. A drop in blood cholesterol may signify that some tumors
are growing as cholesterol provides support for breast cancer
growth," said Frank.
"These data provide new evidence for an increase in cholesterol
utilization by breast tumors and thus provides many new avenues for
prevention, screening, and treatment."
The findings suggest that use of cholesterol-lowering drugs, such
as statins, may both protect against breast cancer as well as treat
patients carrying tumors.
Since researchers also found blood cholesterol levels dropped
significantly as tumors began to develop, the study indicates
measuring blood cholesterol levels may also be an effective method
of screening cancer development.
This research team also discovered the same association between
cholesterol and growth of prostate cancer in mice in a study
published in the December issue of The American Journal of
Pathology.
The results of these two new studies indicate that, according to
Frank, "cholesterol does indeed seem to be an important factor in
the regulation of tumor formation in several cancer types."
