title: Effect of raloxifene on insulin-like growth factor-I, insulin-like growth factor binding protein-3, and leptin in premenopausal women at high risk for developing breast cancer.
abstract: Elevated insulin-like growth factor I (IGF-I) is associated with an increased risk for developing breast cancer in premenopausal women, whereas lower leptin levels have been documented in premenopausal breast cancer cases. We determined the effect of raloxifene on IGF-I, insulin-like growth factor binding protein 3 (IGFBP-3), and leptin in premenopausal women at high risk for developing invasive breast cancer. Twenty-eight premenopausal women (median age 43 years) participating in a pilot breast cancer prevention trial provided 56 matched serum samples. Specimens were collected at baseline and after treatment with 60 mg of raloxifene daily. Median treatment duration was 3 months (range: 6 weeks to 12 months). Samples were frozen at -70 degrees C until analysis. IGF-I, IGFBP-3, and leptin were measured by ELISA. Significance was evaluated by the Wilcoxon signed rank test. Raloxifene administration increased serum IGFBP-3 [mean change 245 ng/ml; P = 0.017; 95% confidence interval (CI), 76-415] and leptin (mean change 2.1 ng/ml; P = 0.005; 95% CI, 0.6-3.7). No significant change in serum IGF-I was detected (mean change 2.6 ng/ml; P = 0.84; 95% CI, -15.4 to 20.6). IGF-I:IGFBP-3 molar ratio was stable (mean change -0.014; P = 0.30; 95% CI, -0.041 to 0.012). Raloxifene administration is associated with an increase in IGFBP-3 and leptin in premenopausal high risk women. Increases in IGFBP-3 may potentially decrease the activity of circulating IGF-I. The effect of modulating the IGF pathway and leptin on breast cancer risk needs additional evaluation.
authors.affiliation: Division of Cancer Prevention and Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1906, USA. engwongj@MAIL.NIH.GOV
authors.forename: Jennifer
authors.initials: J
authors.lastname: Eng-Wong
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Hursting
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Susan N
authors.initials: SN
authors.lastname: Perkins
authors.forename: Jo Anne
authors.initials: JA
authors.lastname: Zujewski
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000187:drug effects* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000187:drug effects* / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008875:Middle Aged; D010865:Pilot Projects; D017697:Premenopause; D011336:Probability; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
chemical_list: D014408:Biomarkers, Tumor; D018972:Insulin-Like Growth Factor Binding Protein 3; D020738:Leptin; D020849:Raloxifene Hydrochloride; D007334:Insulin-Like Growth Factor I