Expression of IGF1R in normal breast tissue and subsequent risk of breast cancer

Abstract

Introduction The growth hormone and insulin-like growth factor (IGF) axis plays an essential role in the growth and development of the mammary gland. IGF1 and IGF1 receptor (IGF1R) may also play a role in the early transformation of mammary cells. Methods Using a nested case-control design, we examined the association between IGF1R expression in normal breast tissue from benign biopsies and subsequent risk of breast cancer within the Nurses’ Health Study. We constructed tissue microarrays (TMAs) containing normal terminal ductal lobular units (TDLUs) from benign breast biopsies. Immunostains for IGF1R were performed on sections cut from the TMAs. A total of 312 women had evaluable IGF1R staining in normal TDLUs; 75 subsequently developed breast cancer (cases) and 237 did not (controls). The epithelial cells in the normal TDLUs were scored for both cytoplasmic and membrane staining for IGF1R. Results Cytoplasmic IGF1R expression was positively associated with subsequent risk of breast cancer (OR=2.47, 95% CI 1.41–4.33). Women whose TDLU epithelial cells showed little or no membrane expression of IGF1R but high levels of cytoplasmic IGF1R were at the highest breast cancer risk and were 15 times more likely to develop subsequent breast cancer when compared with women who had little or no membrane or cytoplasmic IGF1R expression in their TDLU epithelial cells (OR=15.9, 95% CI 3.6–69.8). Conclusion In this study, IGF1R expression patterns in epithelial cells of normal TDLUs in benign breast biopsies were associated with an increased risk of subsequent breast cancer. Additional studies to confirm these findings are necessary.

IGF2 and IGF1R in pediatric adrenocortical tumors: roles in metastasis and steroidogenesis

“…In the IGF1R context, alternative mRNA splicing can lead to distinct protein degradation rates in cancer cells (Mountzios et al 2013) while the frequently expressed isoform (alpha) of IGF1R is not directly associated with global IGF1R gene expression (Pollak 2012). Interestingly, reports have demonstrated the impact of IGF1R protein localization on the biological behavior and prognosis of human breast cancer and in clear renal cancer cells (Aleksic et al 2010, Tamimi et al 2011. The ACT samples presented more IGF1R pure cytoplasmic than mixed cytoplasmic/membranous/nucleus staining, but no significant differences were observed regarding patients' survival, suggesting that IGF1R localization has no prognostic relevance for pediatric ACTs.…”

Plasma carotenoids and the risk of premalignant breast disease in women aged 50 and younger: a nested case–control study

“…Although we did not have information about the ER status of our participants, compared to Bakker et al[33] and Eliassen et al[4], our risk reduction appears to be less than that of ER- tumors but similar or greater than that of ER+. In biopsies of benign breast tissue, Tamimi et al[34] reported that over 90% of the participants were ER+. This supports our data if the majority of our premalignant lesions are ER+.…”

Nurses’ Health Study: demonstrating the impact of research, and adapting new measures and approaches to increase relevance and effect of cohort studies

“…15,16 This latter evaluation showed that a history of breastfeeding was inversely related to basal-like breast cancer. 16 The cohort has also been a rich source of evidence on adiposity in childhood and its relationship to subsequent risk of breast cancer, where it is inversely related to oestrogen receptor-negative breast cancer.…”