Re: Insulin, Insulin-like Growth Factor-I, and Risk of Breast Cancer in Postmenopausal Women

Extract

Gunter et al. ( 1 ) reported results of a large prospective case–control study, confirming that hyperinsulinemia is an independent risk factor for postmenopausal breast cancer. They also discussed a variety of possible mechanisms for breast cancer promotion by hyperinsulinemia and concluded that lowering insulin levels may be a possible strategy for reducing the risk of breast cancer in postmenopausal women.

We strongly agree with these conclusions. However, we would like to comment on some slightly different mechanisms that may better explain the biology of the insulin effect in breast cancer cells and, perhaps, suggest possible strategies for reducing the cancer-promoting effect of insulin. First, it is well recognized that insulin promotes breast cancer cell proliferation (ie, it has mitogenic activity), but there is no evidence that it promotes breast cancer initiation (ie, that it has mutagenic activity). In only a few experimental models is insulin able to induce a transformed phenotype that has some but not all of the characteristics of malignant cells. For example, in both mouse NIH/3T3 fibroblasts ( 2 ) and human 184B5 breast cells in permanent culture ( 3 ), overexpression of the insulin receptor is a prerequisite for insulin-mediated transformation. By contrast, extensive in vitro and in vivo data indicate that insulin may promote breast cancer progression through its mitogenic effect. Therefore, the well-established association between insulin level and breast cancer risk is likely to be the result of hyperinsulinemia promoting growth and progression of subclinical breast cancers rather than a direct effect of insulin on new breast cancer initiation.