Differences in IGF-axis protein expression and survival among multiethnic breast cancer patients

作者：Hernandez Brenda Y^*; Wilkens Lynne R; Le Marchand Loic; Horio David; Chong Clayton D; Loo Lenora W M

来源：Cancer Medicine, 2015, 4(3): 354-362.

DOI：10.1002/cam4.375

• Breast cancer
• IGF1
• IGF1R
• IGFBP2
• IGFBP3
• insulin-axis protein
• multiethnic

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 17years 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.

• 出版日期2015-3