Altered serum levels of insulin-like growth-factor binding proteins in breast cancer patients

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Abstract
Background: Insulin-like growth factor 1 (IGF-1) has mitogenic properties for breast cancer cell lines and has been proposed to be an important factor in breast carcinogenesis. We hypothesized that differences in IGF-1 or its binding proteins might increase susceptibility to breast cancer. This case-control study was designed to investigate whether patients with breast cancer have altered levels of either IGF-1 or its intermediary modulatory proteins, the IGF binding proteins (BP). Methods: Serum was collected from 90 patients (63 with breast cancer and 27 with benign breast disease) after an overnight fast and before surgery. IGF-1, BP1, and BP3 levels were determined by immunoradiometric assays. In a subset of 66 patients, Western ligand blots were also performed for a semiquantitative measurement of functioning BP levels. A forward stepwise logistic regression model to adjust for other confounding variables (age, menopausal status, parity, age at menarche, use of oral contraceptives, history of breast biopsy, family history of breast cancer, hormone replacement therapy, and body-mass index) was used in the multivariate analysis. Results: Serum IGF-1 levels were similar in cases and controls. However, levels of BP3 (ppp2066 ng/ml was 0.18 (95% CI, 0.05–0.55). Correspondingly, women with BP1 levels higher than 39 ng/ml had an odds ratio of 0.21 (95% CI, 0.07–0.68) for breast cancer. When considering only cancer patients (n=63), decreasing levels of BP4 (pppConclusions: Distinct differences in BP profiles exist among patients with breast cancer and also among those with high-grade, hormonal receptor-negative tumors. These findings suggest that the bioavailability of IGF-1 as mediated by its binding proteins may participate in both breast carcinogenesis and selection of more aggressive breast carcinomas.

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