Metabolic Factors May Play A Role In Risk For Breast Cancer

http://www.sciencedaily.com/releases/2009/06/090630132001.htm

ScienceDaily (June 30, 2009) — Physiological changes associated with the
metabolic syndrome may play a role in the risk of postmenopausal breast cancer,
according to study results published in Cancer Epidemiology, Biomarkers &
Prevention, a journal of the American Association for Cancer Research.

The metabolic syndrome, or insulin resistance syndrome, consists of a
constellation of factors including abdominal obesity, high blood glucose levels,
impaired glucose tolerance, abnormal lipid levels and high blood pressure.

Affecting roughly 47 million Americans, the metabolic syndrome is also
associated with poor diet and lack of physical activity. It can also increase
the risk for diabetes and heart disease.

The metabolic syndrome is characterized by elevated insulin levels, and in
recent years scientists have proposed that insulin may contribute directly or
indirectly to the development of breast cancer. Researchers suspect that the
metabolic syndrome could influence the risk for breast cancer by affecting
interrelated hormones, such as insulin, estrogen, cytokines and growth factors.

"This study suggests that having the metabolic syndrome itself or some of its
components may increase a woman's risk of postmenopausal breast cancer. However,
much more work is needed to understand the role of these metabolic factors and
their interplay with better established breast cancer risk factors, such as
reproductive and hormonal factors," said researcher Geoffrey C. Kabat, Ph.D.,
senior epidemiologist in the department of epidemiology and population health at
Albert Einstein College of Medicine, New York.

Studies to date have evaluated individual components of the metabolic syndrome
and breast cancer, with inconsistent results, according to Kabat. For the first
time, Kabat and colleagues assessed whether women who met the criteria of having
the metabolic syndrome were at greater risk for postmenopausal breast cancer.

In this longitudinal study, the researchers used existing data from the Women's
Health Initiative — a large, national study designed to assess major causes of
chronic disease in women. Participants included postmenopausal women aged 50 to
79 years at enrollment who had repeated measurements of components of metabolic
syndrome over an eight-year period. These included blood levels of glucose,
HDL-cholesterol and triglycerides, as well as waist girth and blood pressure.

Results showed a modest positive association of having the metabolic syndrome as
a whole, according to Kabat. Of the 4,888 women with baseline measurements who
did not have diabetes, 165 incident cases of breast cancer were diagnosed during
the follow-up period. Presence of the metabolic syndrome at baseline was not
associated with breast cancer risk.

However, in analyses that made use of the repeated measurements, "women who had
the metabolic syndrome during the three to five years prior to breast cancer
diagnosis had roughly a doubling of risk," he said.

Findings also showed significant associations with elevated blood glucose
levels, triglycerides and diastolic blood pressure. For diastolic blood
pressure, the result was stronger, with more than a two-fold increased risk
(relative risk = 2.4). Generally, for both triglycerides and glucose the
relative risk was about 1.7 for all breast cancer.

"We know a great deal about breast cancer, but we can't identify who is likely
to get it. The effect of different variables associated with increased glucose
and insulin levels needs to be evaluated further in larger studies," Kabat said.
"We need to deepen our understanding of these different interrelated behaviors
and physiological factors to see how they affect breast cancer."

Tim Byers, M.D., M.P.H., associate dean of the Colorado School of Public Health
and interim director of the University of Colorado Cancer Center, believes these
findings are important because the results show possible mechanisms that might
explain the observation that increased weight is a risk factor for
postmenopausal breast cancer.

"We have assumed that the relationship between weight and breast cancer risk is
due to increased circulating estrogens among postmenopausal women who are
overweight or obese," he said. "An alternative explanation is explored here:
that some other aspect of the metabolic syndrome might be involved, such as
growth-stimulating effects of insulin, or insulin-like growth factors."

Based on the results of this study, Byers stated that researchers now need to
look more closely at dynamic changes in insulin over time, in factors tied to
inflammation, and in the specific ways in which estrogen metabolism is tied to
features of the metabolic syndrome.

"Though estrogens are produced in adipose tissues, just how these are
metabolized in various subgroups of women needs better study," he said. "In
addition, the hyper-inflammatory state of obesity and the metabolic syndrome
need to be better described relative to cancer risk."

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