Essential fatty acids, insulin resistance, and breast cancer risk

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.