Premenopausal breast cancer and the association between estrogen receptor status, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and leptin

Abstract

640 Background: The IGF pathway and leptin are associated with breast cancer risk in premenopausal women. These proteins are implicated in breast carcinogenesis through their interactions with the estrogen pathway, potentially resulting in specific breast cancer histopathologic subtypes. Methods: Pretreatment serum IGF-I, IGFBP-3 and leptin levels were examined in newly diagnosed premenopausal breast cancer cases to determine whether an association with tumor estrogen receptor status exists. Odds ratios were determined by logistic regression analysis. Likelihood ratio tests for interaction with BMI were conducted. Results: One hundred and eight women were evaluated (mean age 42); 82 were ER positive and 26 were ER negative. 62 were normal weight (BMI<25) and 46 were overweight and obese (BMI≥25). Mean IGF-I, IGFBP-3 and leptin levels did not differ between the ER positive and ER negative tumors. No associations were found between IGF-I, IGFBP-3 or leptin and ER status of tumors overall or by subset analysis in normal weight versus overweight and obese individuals. A suggestion that elevated IGFBP-3 was associated with ER-negative disease did not reach statistical significance. Additionally, normal-weight women with ER-negative disease had higher leptin levels than their normal-weight ER-positive counterparts, although we lacked statistical power to detect an effect of BMI on the association between leptin levels and tumor hormone receptor status. Conclusions: This is the first report examining the IGF pathway and leptin in relation to ER status in premenopausal women with newly diagnosed breast cancer. Our small number of cases suggests a number of intriguing findings that should be evaluated in larger studies. Determining links between ER status and IGFBP-3 and leptin may help better define risk factors and potentially appropriate interventions for ER-negative versus ER-positive breast cancer. No significant financial relationships to disclose.