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Table 2 Overview of in vivo studies in animals on the correlation of insulin analogues and breast cancer

From: Treatment with insulin (analogues) and breast cancer risk in diabetics; a systematic review and meta-analysis of in vitro, animal and human evidence

Author, year Model Number of animals per treatment group Tissues analysed Time points sampling Analogues tested Dose tested nM Method Proteins analysed Carcinogenic potential Sig. Tumour characteristics
Stammberger et al., 2002 [37] (re-evaluation in 2012) [38] Sprague–Dawley rats and Wistar rats and NMRI mice 5−30 No further tumour characterisation Follow up of 2 years Glargine 2, 5, 12.5 IU/Kg Spontaneous mammary gland tumour formation upon treatment   -   MG adenoma, fibroadenoma, adenocarcinoma
Gallagher et al., 2012 [36] Orthotopic mammary tumour weight and hyperinsulinaemic MKR mice 3−4 Mammary gland 0−25 days AspB10 12.5 IU/kg Tumour volume measurement   Yes  
Lung metastasis 2x/day Counting lung metastases   No  
WB receptor activation p-INSR Yes  
p-IGF1R   
p-Akt Yes
p-Erk -  
Tennagels et al., 2013 [39] Female Sprague–Dawley rats 3−4 Mammary gland 60 min Glargine 12.5, U/kg WB kinase activation p-INSR -   
AspB10    p-IGF1R Yes
Ter Braak et al., 2015 [40] p53R270H/+WAPCre FVB mice 40 Mammary gland tumors Chronic exposure till MG tumor development Glargine 12.5-15 IU/kg Tumour latency time   No Majority aggressive EMT no correlation pathology and treatment
AspB10 150-200 IU/kg    Yes
WB protein expression profiling INSR    
IGF1R,
Erk,
p-Erk, Yes
Akt,   
p-Akt, Yes
EGFR,
ER,
E-cad,
N-cad, Her2
  1. IGF1R insulin-like growth factor-1 receptor, EGFR epidermal growth factor receptor, ERK extracellular signal-related kinase, ER oestrogen receptor, E-cad E-cadherin, N-cad N-cadherin, Her2 human epithermal growth factor receptor 2