This review compares the prevalence of hyperinsulinemic
insulin resistance in Caucasian-American women with that in Japanese-American and Pima Indian minority groups in the United States. It also examines the differences in
breast cancer risk between these ethnic groups and suggests that risk may be modulated by ethnic
genetic susceptibility to the effect of the Western diet in precipitating
insulin resistance. It is widely agreed that the Western diet with its high
saturated fatty acid content and high n-6/n-3 ratio of
polyunsaturated fatty acids (PUFAs) favors the manifestation of
hyperinsulinemia in individuals who are genetically predisposed. A number of case-control studies have shown
hyperinsulinemia to be a marker of increased
breast cancer risk, particularly in obese postmenopausal women. Mechanisms that have been postulated include an increased sex
steroid level associated with a decreased serum level of
sex hormone-binding globulin and an increased bioactive level of
insulin-like growth factor I, which may synergize with
estrogen in promoting mammary
carcinogenesis. Dietary supplements rich in n-3 PUFAs have been shown to inhibit the growth of human
breast cancer implants in nude mice, and members of the
n-3 PUFA series can inhibit the growth of human
breast cancer cell lines in vitro. On the basis of this experimental evidence, some have proposed dietary supplements rich in n-3 PUFAs for
breast cancer protection. However, increased consumption of PUFAs requires increased intake of
antioxidants.
Vitamin E may be the most suitable agent, especially because of its added advantage that in animal models it is reported to reduce the incidence of
carcinogen-induced mammary
tumors. Preliminary trials of the combination may best be planned as adjuvant treatment after primary surgery for
breast cancer, and the
insulin hypothesis could be tested in the trials by monitoring fasting
insulin and sex
steroid levels.