A report just published in the Journal of the National Cancer Institute adds more evidence to the importance of insulin regulation in ER (estrogen receptor) negative breast cancer. The authors first note a conundrum in breast cancer epidemiology:

“Body mass index is inversely associated with risk of premenopausal breast cancer, but the underlying mechanisms for this association are poorly understood. Abdominal adiposity is associated with metabolic and hormonal changes, many of which have been associated with the risk of premenopausal breast cancer.”

They investigated the association between body fat distribution, hip circumference, and waist to hip ratio, and the incidence of premenopausal breast cancer in the Nurses’ Health Study II:

“During 426 164 person-years of follow-up from 1993 to 2005, 620 cases of breast cancer were diagnosed among 45 799 women. Hormone receptor status information was available for 84% of the breast cancers.”

When they looked at the group as a whole, no statistically significant associations were found. However…

“…each of the three body fat distribution measures was statistically significantly associated with greater incidence of estrogen receptor (ER)–negative breast cancer.”

The risk for ER-negative breast cancer was increased by 275% for waist circumference, 240% for hip circumference, and 195% for waist to hip ratio (comparing the highest to the lowest quintile). The authors state:

“These findings may suggest that an insulin-related pathway of abdominal adiposity is involved in the etiology of premenopausal breast cancer.“

The implication is that factors associated with increased abdominal adiposity influence the development of breast cancer through estrogen independent pathways, specifically the influence of excess levels of insulin on tumor growth that also promote the accumulation of fat around the waist. As experienced clinicians know, tumors often have mixed cell types. The role of insulin as a tumor promoter should never overlooked in case management, with careful attention to the regulation of blood sugar and insulin.

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Factors that place fat around the waist (insulin resistance) and the activity of that fat tissue (production of signaling molecules that promote inflammation) are both at play behind the connection documented recently in this paper published in the journal Neurology. The authors found that “…a midlife WHR [waist hip ratio] greater than 0.80 increased risk for dementia approximately twofold…,” and conclude: “There are midlife and late-life implications for dementia prevention, and analytical considerations related to identifying risk factors for dementia.” Here are a few more papers related to the same finding:

1. Research on diabetes, hyperinsulinemia and dementia in Dementia and Geriatric Disorders
2. A paper on abdominal obesity and Alzheimer Disease published in the same journal
3. A study in Archives of Neurology that concludes: “A larger WHR may be related to neurodegenerative, vascular, or metabolic processes that affect brain structures underlying cognitive decline and dementia.”

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