As each insulin analogue has different alterations in the amino acid sequence, the pharmacologic properties of the analogues are slightly different. This may result in increased mitogenic action of insulin analogues. However, structural transformation of human insulin might also result in different binding affinity towards the insulin-like growth factor-1 (IGF-1) receptor (IGF1R). These modifications afford greater flexibility in the treatment of diabetic patients. Insulin analogues have been marketed since 1997 and are different from the human insulin molecule in that the amino acid sequence is modified to have an altered pharmacokinetic profile. Gradually animal insulin has been almost completely replaced by modified or biosynthetic human insulin, such as NPH, Lente or Regular, and insulin analogues. The initial source of insulin for clinical use in humans was from animal pancreas. Insulin can act as a growth factor, and it is biologically plausible that use of exogenous insulin (analogues), could stimulate neoplastic growth. However, it is unknown if this association is due to the high blood glucose levels of DM, hyperinsulinaemia, shared risks factors such as obesity, or side-effects of diabetic treatment.Įxogenous insulin treatment for diabetics includes animal insulin, human insulin and insulin analogues. Diabetes mellitus (DM) has been associated with breast cancer. Overall, the data suggests that insulin treatment is not involved in breast tumour initiation, but might induce breast tumour progression by up regulating mitogenic signalling pathways.īreast cancer is the most prevalent cancer in women with 1.67 million new cancer cases diagnosed in 2012 worldwide. There is no compelling evidence that any clinically available insulin analogue (Aspart, Determir, Glargine, Glulisine or Lispro), nor human insulin increases breast cancer risk. It has to be taken into account that the number of animal studies was limited, and epidemiological studies were underpowered and suffered from methodological limitations. However, the pooled analysis of 13 epidemiological studies did not show evidence for an association between insulin glargine treatment and an increased breast cancer risk (HR 1.04 95 % CI 0.91-1.17 p=0.49) versus no glargine in patients with diabetes mellitus.
Glargine was the only clinically available insulin analogue for which an increased proliferative potential was found in breast cancer cell lines. Insulin AspB10 showed mitogenic properties in vitro and in animal studies. In total 16 in vitro, 5 animal, 2 in vivo human and 29 epidemiological papers were included. Protein and gene expression was analysed for the cell lines most frequently used in the included in vitro studies. A comprehensive overview was composed for in vitro and animal studies. A quantitative and qualitative review was performed on the epidemiological data due to a limited number of reported estimates, a meta-analysis was performed for glargine only. MethodĪ systematic literature search was performed on breast cell-line, animal and human studies using the key words ‘insulin analogue’ and ‘breast neoplasia’ in MEDLINE at PubMed, EMBASE, and ISI Web of Science databases. The aim of this study was to review the postulated association between insulin and insulin analogue treatment and breast cancer development, and plausible mechanisms. Several studies have suggested that anti-diabetic insulin analogue treatment might increase cancer risk.
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