Insulin-like growth factor (IGF)-I and IGF-II serum concentrations in patients with benign and malignant breast lesions: free IGF-II is correlated with breast cancer size

Purpose: Insulin-like growth factors (IGFs) are potent mitogens for breast cancer cells in vitro, and elevated IGF-I serum levels are a risk factor for breast malignancies. This study evaluated IGF-I and IGF-II serum levels in healthy women and in patients with benign and malignant breast lesions and correlated them with tumor size. Experimental Design: Serum levels of the total and unbound fractions of IGF-I and IGF-II were analyzed in 65 patients with benign and malignant breast lesions and in 38 women without breast disease. ELISAs were used to detect serum IGF levels, with (total IGF) or without (free IGF) prior acid-ethanol extraction. Results: Total IGF-I serum concentrations were lower in healthy women than in breast cancer patients (P < 0.001) or patients with benign breast lesions (P = 0.010), but no differences were observed in free IGF-I levels. Conversely, healthy women had higher serum levels of free IGF-II than women with breast lesions (P = 0.003), and the free/total IGF-II ratio was significantly reduced in patients with breast disease (P = 0.001). Although IGF-I or IGF-II serum concentrations of breast cancer patients were similar to those of patients with benign lesions, the size of a malignant tumor was correlated to the ratio free/total IGF-II (P = 0.002). Conclusions: Malignant breast tumors cannot be distinguished from benign breast lesions by systemic IGF serum levels. However, women with breast lesions have decreased IGF-II concentrations, and free IGF-II levels are clearly correlated to the size of a breast cancer, indicating an involvement in tumor growth.