WHI: Hyperinsulinemia Mediates Obesity's Breast Cancer Risk

[Hopeful]

DENVER (EGMN) - New data from the Women's Health Initiative indicate that hyperinsulinemia is an independent risk factor for breast cancer.
This observation goes a long way toward explaining the well-established association between obesity and increased breast cancer risk, Marc J. Gunter, Ph.D., asserted at the annual meeting of the American Association for Cancer Research.
The clinical implication is that interventions that are designed to reduce high fasting insulin levels may decrease a woman's risk of breast cancer. This could be accomplished in a variety of ways: through drugs, weight loss, or increased physical activity, added Dr. Gunter, an epidemiologist at Albert Einstein College of Medicine, New York.
The new findings regarding hyperinsulinemia as a breast cancer risk factor take on particular urgency in light of the ongoing obesity epidemic in the United States. With more than one-third of women now categorized as obese and another third as overweight, there is a concern that the incidence of breast cancer may soon increase.
Dr. Gunter presented a prospective case-cohort study conducted in a subset of participants in the Women's Health Initiative Observational Study (WHI-OS), which included 93,676 postmenopausal women aged 50-79 years.
His study population consisted of 835 randomly selected nondiabetic WHI-OS participants who were diagnosed with breast cancer after more than 1 year of follow-up, and 816 controls who did not develop breast cancer during a mean 77 months of follow-up. Baseline serum levels of fasting insulin, estradiol, glucose, free and total insulinlike growth factor 1 (IGF-1), and insulinlike growth factor binding protein-3 were available for all subjects.
Among nonusers of hormone therapy (HT), women in the highest quartile of fasting insulin level had a highly significant 2.4-fold greater risk of breast cancer than did those in the lowest quartile, after researchers controlled for established breast cancer risk factors, including serum estradiol.
No association was noted between fasting insulin level and breast cancer risk in HT users, possibly because fasting insulin levels were significantly lower in HT users than nonusers. Also, oral HT exposes the liver to large doses of estrogen, altering hepatic protein synthesis.
The link between obesity and breast cancer has previously been thought to be mainly the result of high levels of circulating estrogen present in heavy women. An advantage of the WHI-OS design, Dr. Gunter noted, is that it's possible to control for endogenous estradiol levels and thereby isolate fasting insulin's impact on breast cancer risk. In this study, obesity was associated with a 2.1-fold increased risk of breast cancer, compared with a body mass index of 18.5-24.9 kg/m². However, this relationship was greatly attenuated by adjusting for insulin level and, to a lesser extent, by adjusting for serum estradiol.
In this study, an increased serum estradiol level was associated with a greater risk only of hormone receptor-positive breast cancers. Neither free nor total IGF-1 levels were associated with breast cancer risk.
The WHI program is funded by the National Heart, Lung, and Blood Institute.

Hopeful