Differences in IGF‐axis protein expression and survival among multiethnic breast cancer patients. (26th January 2015)

• Record Type: Journal Article
• Authors: Hernandez, Brenda Y.; Wilkens, Lynne R.; Le Marchand, Loïc; Horio, David; Chong, Clayton D.; Loo, Lenora W. M.
• Is Part Of: Cancer medicine. Volume 4:Number 3(2015:Mar.)
• Page Start: 354
• Page End: 362
• Publication Date: 2015-01-26
• Subjects: Breast cancer -- IGF1 -- IGF1R -- IGFBP2 -- IGFBP3 -- insulin‐axis protein -- multiethnic; 616.994005
• DOI: 10.1002/cam4.375
• Languages: English
• ISSNs: 2045-7634

Abstract

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: HRmort = 10.96, 95% CI: 2.18–55.19 and HRmort = 35.75, 95% CI: 3.64–350.95, respectively; IGFBP3: HRmort = 5.16, 95% CI: 1.27–20.94 and HRmort = 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. Abstract : The relationship of (insulin‐like growth factor) IGF1, IGF1R, IGFBP2 (IGF‐binding proteins2), and IGFBP3 expression in breast tumor tissue with survival was examined in a multiethnic population. In Native Hawaiian patients, IGFBP2 and IGFBP3, and IGF1R expression were predictors of poor survival. No association of IGF‐axis protein expression and survival was observed in Japanese or Caucasian patients.