Purpose: The insulin-like growth factor (IGF) signaling system is involved in breast cancer initiation and progression. The prognostic relevance of tumor expression patterns of IGFI-related proteins remains poorly understood. This study associates the expression of selected IGF proteins with breast tumor and patient characteristics.Experimental Design: IGFI, IGFI receptor, IGF-binding protein (IGFBP)2, and IGFBP3 expression was measured in 855 primary breast carcinomas by immunohistochemistry using tissue microarrays. We investigated the association of tumor and nodal stage, grade, hormone receptor status, HER2 gene amplification, menopausal status, body mass index, and survival with IGF protein expression.Results: In contrast to IGFI, the expression of IGFI receptor, IGFBP2, and IGFBP3 was associated with estrogen receptor status. In addition, IGFBP3 was positively correlated with body mass index and premenopausal status. Importantly, IGFBP2 was an independent and positive predictor of overall survival (hazard ratio, 0.48; 95% confidence interval, 0.24-0.95; P = 0.04). There was a weak suggestion for IGFBP2 and overweight to modify each other's effect on survival.Conclusions: According to these results, which need confirmation in larger patient series, the prognostic relevance of IGFBP2 and IGFBP3 protein expressions in breast cancer may depend on the hormonal context and body weight. Clin Cancer Res; 16(3); 1025-32. ©2010 AACR.Understanding the biology of breast cancer progression is an important aspect of identifying therapeutic targets. Both obesity at diagnosis and subsequent weight gain are predictive of worse breast cancer survival (1). The obesity-breast cancer association may in part be related to hyperinsulinemia, the concomitant decrease in insulin-like growth factor (IGF)-binding proteins (IGFBP)1 and IGFBP2, and the resulting increase in bioactive IGFI (2). IGFI and IGF2 play a role in mammary gland development (3-5). They have mitogenic, antiapoptotic, and proangiogenic effects and stimulate the motility of breast cancer cells in vitro (3). The two growth factors act through IGFI receptor (IGFIR) homodimerization (3). Their bioavailability in circulation and tissues is regulated by at least six IGF-binding proteins. IGFBP3 and IGFBP2 are the most abundant IGFBPs in the blood. In addition to regulating IGF activity, IGFBPs exert additional IGF-independent effects (6).Transgenic mice deficient in IGFI exhibit a decreased susceptibility to mammary carcinogens (7). Tumor incidence is increased in mice expressing IGFI or IGF2 in the mammary gland (3). According to several meta-analyses and systematic reviews, circulating concentrations of IGFI and less consistently of IGFBP3 were positively associated with premenopausal breast cancer (8). Much less is known about the prognostic relevance of autocrine and paracrine IGF signaling in tumor tissue. Several breast cancer studies reported on the correlation between estrogen receptor (ER) status and the expression patterns of IGF-related proteins (9-12...

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Supplementary Data from IGFBP2 and IGFBP3 Protein Expressions in Human Breast Cancer: Association with Hormonal Factors and Obesity

<div>Abstract<p><b>Purpose:</b> The insulin-like growth factor (IGF) signaling system is involved in breast cancer initiation and progression. The prognostic relevance of tumor expression patterns of IGFI-related proteins remains poorly understood. This study associates the expression of selected IGF proteins with breast tumor and patient characteristics.</p><p><b>Experimental Design:</b> IGFI, IGFI receptor, IGF-binding protein (IGFBP)2, and IGFBP3 expression was measured in 855 primary breast carcinomas by immunohistochemistry using tissue microarrays. We investigated the association of tumor and nodal stage, grade, hormone receptor status, <i>HER2</i> gene amplification, menopausal status, body mass index, and survival with IGF protein expression.</p><p><b>Results:</b> In contrast to IGFI, the expression of IGFI receptor, IGFBP2, and IGFBP3 was associated with estrogen receptor status. In addition, IGFBP3 was positively correlated with body mass index and premenopausal status. Importantly, IGFBP2 was an independent and positive predictor of overall survival (hazard ratio, 0.48; 95% confidence interval, 0.24-0.95; <i>P</i> = 0.04). There was a weak suggestion for IGFBP2 and overweight to modify each other's effect on survival.</p><p><b>Conclusions:</b> According to these results, which need confirmation in larger patient series, the prognostic relevance of IGFBP2 and IGFBP3 protein expressions in breast cancer may depend on the hormonal context and body weight. Clin Cancer Res; 16(3); 1025–32</p></div>

<div>Abstract<p><b>Purpose:</b> The insulin-like growth factor (IGF) signaling system is involved in breast cancer initiation and progression. The prognostic relevance of tumor expression patterns of IGFI-related proteins remains poorly understood. This study associates the expression of selected IGF proteins with breast tumor and patient characteristics.</p><p><b>Experimental Design:</b> IGFI, IGFI receptor, IGF-binding protein (IGFBP)2, and IGFBP3 expression was measured in 855 primary breast carcinomas by immunohistochemistry using tissue microarrays. We investigated the association of tumor and nodal stage, grade, hormone receptor status, <i>HER2</i> gene amplification, menopausal status, body mass index, and survival with IGF protein expression.</p><p><b>Results:</b> In contrast to IGFI, the expression of IGFI receptor, IGFBP2, and IGFBP3 was associated with estrogen receptor status. In addition, IGFBP3 was positively correlated with body mass index and premenopausal status. Importantly, IGFBP2 was an independent and positive predictor of overall survival (hazard ratio, 0.48; 95% confidence interval, 0.24-0.95; <i>P</i> = 0.04). There was a weak suggestion for IGFBP2 and overweight to modify each other's effect on survival.</p><p><b>Conclusions:</b> According to these results, which need confirmation in larger patient series, the prognostic relevance of IGFBP2 and IGFBP3 protein expressions in breast cancer may depend on the hormonal context and body weight. Clin Cancer Res; 16(3); 1025–32</p></div>

Supplementary Data from IGFBP2 and IGFBP3 Protein Expressions in Human Breast Cancer: Association with Hormonal Factors and Obesity