Expression of estrogen receptors in non-malignant mammary tissue modifies the association between insulin-like growth factor 1 and breast cancer risk

Background: Several studies have reported that the insulin-like growth factor 1 (IGF-1) is positively associated with estrogen receptor-positive [ER(+)] breast cancer risk, whereas there is little or no association with respect to ER(-) breast cancer. All comparisons of ER(+) breast cancer cases, however, have been made versus healthy controls, for whom there is no information about the ER expression in their mammary gland. Patients and methods: In the context of a case-control investigation conducted in Athens, Greece, we studied 102 women with incident ER alpha(+) breast cancer and compared their IGF-1 blood levels with those of 178 ER alpha(+) and 83 ER alpha(-) women with benign breast disease (BBD) who underwent biopsies in the context of their standard medical care. Data were analysed using multiple logistic regression and controlling for potential confounding variables. Results: ER alpha(+) breast cancer patients had higher IGF-1 levels compared with women with BBD [odds ratio (OR) 1.36, 95% confidence interval (CI): 0.95-1.94, per 1 standard deviation (SD) increase in IGF-1 levels]. When ER alpha status of women with BBD was taken into account, the difference in IGF-1 levels between ER alpha(+) breast cancer patients and women with BBD was clearly driven by the comparison with BBD women who were ER alpha(+) (OR = 1.95, 95% CI: 1.31-2.89 per 1 SD increase in IGF-1 levels), whereas there was essentially no association with IGF-1 levels when ER alpha(+) breast cancer patients were compared with ER alpha(-) BBD women. These contrasts were particularly evident among post/peri-menopausal women. Conclusion(s): We found evidence in support of an interaction of IGF-1 with the expression of ER alpha in the non-malignant mammary tissue in the context of breast cancer pathogenesis. This is in line with previous evidence suggesting that IGF-1 increases the risk of ER(+) breast cancer.