title: Associations of insulin-like growth factor and insulin-like growth factor binding protein-3 with mortality in women with breast cancer.
abstract: Elevated circulating insulin-like growth factor-1 (IGF-1), a breast epithelial cell mitogen, is associated with breast cancer development. However, its association with breast cancer survival is not established. Circulating concentrations of IGF-1 are controlled via binding proteins, including IGF Binding Protein-3 (IGFBP-3), that may modulate the association of IGF-1 with breast-cancer outcomes. We measured IGF-1 and IGFBP-3 concentrations in serum from 600 women enrolled in the health, eating, activity, and lifestyle (HEAL) study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between IGF-1 and IGFBP-3, and as a ratio, modeled using quintile cut-points, with risk of breast cancer-specific (n = 42 deaths) and all-cause mortality (n = 87 deaths) using Cox proportional hazards models. In models adjusted for body mass index, ethnicity, tamoxifen use at time of blood draw, treatment received at diagnosis and IGFBP-3, women in the highest quintile of IGF-1 level had an increased risk of all-cause mortality (Hazard Ratio (HR) = 3.10, 95% CI 1.21-7.93, p = 0.02), although no dose-response association was evident. The IGF-1/IGFBP-3 ratio, an indicator of free IGF-I levels, was significantly associated with increasing risk of all-cause mortality (HR = 2.83, 95% CI 1.25-6.36 p(trend)  = 0.01, upper vs. lower quintile) in a fully adjusted model. In conclusion, high serum levels of IGF-1 and the IGF-1/IGFBP-3 ratio were associated with increased risk of all-cause mortality in women with breast cancer. These results need to be confirmed in larger breast cancer survivor cohorts.
authors: Fred Hutchinson Cancer Research Center, Public Health Sciences, Seattle, WA. cduggan@fhcrc.org.
authors: Catherine
authors: C
authors: Duggan
authors: Ching-Yun
authors: CY
authors: Wang
authors: Marian L
authors: ML
authors: Neuhouser
authors: Liren
authors: L
authors: Xiao
authors: Ashley Wilder
authors: AW
authors: Smith
authors: Kerryn W
authors: KW
authors: Reding
authors: Richard N
authors: RN
authors: Baumgartner
authors: Kathy B
authors: KB
authors: Baumgartner
authors: Leslie
authors: L
authors: Bernstein
authors: Rachel
authors: R
authors: Ballard-Barbash
authors: Anne
authors: A
authors: McTiernan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood* / Q000401:mortality*; D002140:California / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008875:Middle Aged; D009516:New Mexico / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D018426:SEER Program; D014861:Washington / Q000453:epidemiology
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I