Obesity during menopause promotes breast tumour growth and progression
Obese women might be able to eliminate their increased risk for postmenopausal breast cancer by taking measures during perimenopause to prevent weight gain and to therapeutically control the metabolic effects of their obesity, researchers say.
"Obese postmenopausal women have increased risk for breast cancer and poorer clinical outcomes compared with postmenopausal women who are lean," Paul S. MacLean from the University of Colorado Anschutz Health and Wellness Center in Aurora, Colo, said.
"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," he said.
During menopause, women often gain weight because they consume more food than their body needs.
In a previous study, MacLean and colleagues used their rat model to show that weight gain following surgical ovariectomy, which models menopause, helped promote breast tumour development in obese rats.
In this study, they confirmed that obesity and overfeeding after surgical ovariectomy together drove aggressive tumour growth and progression.
One reason was that obese rats were unable to appropriately 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 tumours dramatically increased uptake of glucose.
A second reason for the enhanced tumour growth and progression in obese rats compared with lean rats was that tumours from the two groups of animals had different molecular profiles. Tumours from 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 tumours from postmenopausal women. According to MacLean, a final piece of evidence indicating that obesity and overfeeding during the menopausal transition converge to promote tumour growth and progression was that the antidiabetic drug metformin reduced tumour burden 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," MacLean said.
"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," he added.
The study has been published in the journal Cancer Research.