title: Differences in IGF-axis protein expression and survival among multiethnic breast cancer patients.
abstract: There is limited knowledge about the biological basis of racial/ethnic disparities in breast cancer outcomes. Aberrations in IGF signaling induced by obesity and other factors may contribute to these disparities. This study examines the expression profiles of the insulin-like growth factor (IGF)-axis proteins and the association with breast cancer survival across a multiethnic population. We examined the expression profiles of the IGF1, IGF1R, IGFBP2 (IGF-binding proteins), and IGFBP3 proteins in breast tumor tissue and their relationships with all-cause and breast cancer-specific survival up to 17 years postdiagnosis in a multiethnic series of 358 patients in Hawaii, USA. Native Hawaiians, Caucasians, and Japanese were compared. Covariates included demographic and clinical factors and ER/PR/HER2 (estrogen receptor/progesterone receptor/human epidermal growth factor receptor-2) status. In Native Hawaiian patients, IGFBP2 and IGFBP3 expression were each independently associated with overall and breast cancer mortality (IGFB2: HR(mort) = 10.96, 95% CI: 2.18-55.19 and HR(mort) = 35.75, 95% CI: 3.64-350.95, respectively; IGFBP3: HR(mort) = 5.16, 95% CI: 1.27-20.94 and HR(mort) = 8.60, 95% CI: 1.84-40.15, respectively). IGF1R expression was also positively associated with all-cause mortality in Native Hawaiians. No association of IGF-axis protein expression and survival was observed in Japanese or Caucasian patients. The interaction of race/ethnicity and IGFBP3 expression on mortality risk was significant. IGF-axis proteins may have variable influence on breast cancer progression across different racial/ethnic groups. Expression of binding proteins and receptors in breast tumors may influence survival in breast cancer patients by inducing aberrations in IGF signaling and/or through IGF-independent mechanisms. Additional studies to evaluate the role of the IGF-axis in breast cancer are critical to improve targeted breast cancer treatment strategies.
authors.affiliation: University of Hawaii Cancer Center, University of Hawaii, Honolulu, Hawaii.
authors.forename: Brenda Y
authors.initials: BY
authors.lastname: Hernandez
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.forename: David
authors.initials: D
authors.lastname: Horio
authors.forename: Clayton D
authors.initials: CD
authors.lastname: Chong
authors.forename: Lenora W M
authors.initials: LW
authors.lastname: Loo
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000378:metabolism*; D005006:Ethnicity; D005260:Female; D006254:Hawaii / Q000453:epidemiology / Q000208:ethnology; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008875:Middle Aged; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000378:metabolism*
chemical_list: C583557:IGF1 protein, human; C000597236:IGF1R protein, human; C577903:IGFBP2 protein, human; C515497:IGFBP3 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: Breast cancer; IGF1; IGF1R; IGFBP2; IGFBP3; insulin-axis protein; multiethnic