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: 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.

Current advances in biomarkers for targeted therapy in triple-negative breast cancer

“… 34 In addition, IGFBP2 was found to be a predictor of recurrence-free survival (RFS) when measured along with four other proteins in TNBC patients receiving post-neoadjuvant chemotherapy. 60 However, a report by Hernandez et al 61 in 2015 disagreed with the findings. Hernandez et al examined the relationship between IGF and IGFBP expression with survival rates in Asian, Pacific Islander, and Caucasian patients and found that increased IGFBP2 expression correlated to a decreased breast cancer survival rate, and the increased IGFBP2 expression varied between racial/ethnic groups.…”

The Insulin-like Growth Factor Axis, Adipokines, Physical Activity, and Obesity in Relation to Breast Cancer Incidence and Recurrence

“…It is likely that, in addition to a variety of social, structural, and environmental factors, biological factors influence how breast cancer is expressed ( Coughlin & Cypel, 2013 ). Alterations in IGF signaling induced by obesity and/or other factors may lead to these disparities ( Hernandez et al, 2015 ). However, there is currently a paucity of health intervention studies that include sizeable numbers of African American or Hispanic breast cancer survivors.…”

“…IGF-1R positivity reflects a well-differentiated tumor with low metastatic tendency ( Aaltonen et al, 2014 ). Among women with triple-negative breast cancers, IGF-1R is a predictor of poorer survival ( Hernandez et al, 2015 ). Hernandez et al (2015) examined the expression of proteins in the IGF axis and the association with breast cancer survival.…”

“…Among women with triple-negative breast cancers, IGF-1R is a predictor of poorer survival ( Hernandez et al, 2015 ). Hernandez et al (2015) examined the expression of proteins in the IGF axis and the association with breast cancer survival. In Native Hawaiian patients, IGFBP-2 and IGFBP-3 expression were each independently associated with overall and breast cancer mortality.…”

“…In Native Hawaiian patients, IGFBP-2 and IGFBP-3 expression were each independently associated with overall and breast cancer mortality. IGF-1R expression was also positively associated with overall mortality in Native Hawaiians ( Hernandez et al, 2015 ). In Japanese or Caucasian patients, however, no association of expression of IGF proteins and survival was observed.…”