Obesity and Overeating During Menopause Promote Breast Tumor Growth and Progression

A new study has found a way for obese women to curb the increased risk of postmenopausal breast cancer.

According to a new study conducted at the University of Colorado Anschutz Health and Wellness Center in Aurora, Colo. obese women should take proper measures during perimenopause to prevent weight gain and to therapeutically control the metabolic effects of their obesity.

"Obese postmenopausal women have increased risk for breast cancer and poorer clinical outcomes compared with postmenopausal women who are lean," said Paul S. MacLean, Ph.D., associate professor of medicine at the University of Colorado Anschutz Health and Wellness Center. "The reasons for this are not fully understood.

"Unfortunately you cannot do the studies needed to address this issue in humans. So, we merged rat models of obesity, breast cancer and menopause to best mimic the events that link premenopausal obesity to an increased rate of postmenopausal breast cancer."

It is well known that women  suffer a sudden increase in the body weight because they consume more food than their body needs. 

MacLean and colleagues, in a previous study, used rat models to show that weight gain following surgical ovariectomy, which models menopause, helped promote breast tumor development in obese rats.

Whereas in this study it was confirmed that obesity and overfeeding after surgical ovariectomy together drove aggressive tumor growth and progression.

The reason was obese rats were unable to handle the excess sources of energy, in the form of glucose and dietary fat, which accumulated as a result of overfeeding after surgical ovariectomy. 

Lean rats stored the excess glucose and dietary fat from overfeeding in liver, fat, muscle and healthy breast tissue, a normal metabolic response to overfeeding. In contrast, the healthy tissues in obese rats failed to increase uptake of glucose and dietary fat, but the breast tumors dramatically increased uptake of glucose.

Secondly, the enhanced tumor growth and progression in obese rats was due to the difference in molecular profiles. Tumor in obese rats had higher levels of expression of the progesterone receptor (PR), which was related to higher expression of genes involved in energy use and proliferation.

A similar pattern of increased expression of genes involved in energy use and cell growth was seen in human PR-positive breast tumors from postmenopausal women. He also noticed that the antidiabetic drug metformin reduced tumor load in obese rats after surgical ovariectomy.  

 "If our findings in rats translate to humans, it means that the perimenopausal period is a critical window of time for determining breast cancer risk later in life," said MacLean. "This, in turn, means that an obese woman's risk for postmenopausal breast cancer and poor clinical outcome could be reduced by perimenopausal lifestyle modifications, such as restricting food consumption and increasing exercise, and/or perimenopausal use of drugs, such as metformin, to improve metabolic control."

The study was published in the journal American Association for Cancer Research.