Obesity during menopause stops healthy tissue from trapping excess fat and sugars, which instead fuel tumor growth.
Obese, postmenopausal women are at greater risk for developing breast cancer and their cancers tend to be more aggressive than those in lean counterparts. A University of Colorado Cancer Center study published in the December issue of the journal Cancer Research shows how this risk might be prevented.
By using nutrient tracers for fat and sugar, the researchers tracked where the body stored excess calories. In lean mice models, excess fat and glucose were taken up by the liver, mammary and skeletal tissues. In obese mice models, excess fat and glucose were taken up by tumors, fueling their growth.
In short, if you are lean, excess calories go to healthy tissue. If you are obese, excess calories feed the tumor.
This implies that the menopausal window may be an opportunity for women to control their breast cancer risk through weight management, the researchers said.
The study also showed that tumors from obese animals had increased levels of the progesterone receptor, and this receptor appears to give tumors a metabolic advantage for growth.
To extend their findings to humans, they analyzed 585 human breast cancers and found that human tumors expressing the progesterone receptor had the same metabolic advantage.
They saw an abnormal metabolic response to fat and sugar in the obese animals that, in many ways, mirrors the response to fat and sugar in Type 2 diabetes. Noticing this similarity, the group tested the use of the common Type 2 diabetes drug, Metformin, in their model of postmenopausal breast cancer.
With drug treatment, tumor size was dramatically decreased in the obese, and tumors showed reduced expression of the progesterone receptor.
Using a model, the investigators found that weight gain during menopause is particularly bad for those who are obese when entering menopause.
Together, the results of this study suggest that the combination of obesity and weight gain during menopause can impact breast cancer in two ways. First, tumors that arise in obese women appear to have a metabolic advantage, and second, the inability to store excess calories in healthy tissues may further fuel tumor growth.
"While drugs may be useful in controlling breast cancer risk in obese, postmenopausal women, our results imply that a combination of diet and exercise may be equally if not more beneficial," the researcher said.
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