Measuring IGF-1, ER-α and EGFR expression can predict tamoxifen-resistance in ER-positive breast cancer.

In vitro studies have suggested that tamoxifen resistance may be due to altered expression and downstream signalling of insulin-like growth factor-1 (IGF-1) receptor (IGF-1l), oestrogen receptor-alpha (ERα), epidermal growth factor receptor (EGFR) and HER-2. We investigated which gene expressions could predict tamoxifen resistant breast cancer. Expression of IGF-1R, IGF-1 ligand (IGF-1), ERα, EGFR and HER-2 in 91 ER-positive breast cancer tumours were measured using real-time PCR and correlated with clinical outcome. The tamoxifen resistant group (n=20) consisted of: i) tumours which were resistant to neoadjuvant tamoxifen treatment and ii) tumours which were excised from patients who later developed recurrence or metastasis during adjuvant tamoxifen treatment. These were compared with tamoxifen sensitive tumours which were surgical excision specimens from patients who did not develop recurrence/metastasis during adjuvant tamoxifen treatment. Tumours with higher IGF-1 ligand and ERα expression took longer to develop tamoxifen resistance. Tamoxifen resistant tumours had lower IGF-1 and ERα expression compared to tamoxifen-sensitive tumours. IGF-1 expression strongly correlated with ERα expression in the tamoxifen sensitive group only. ERα inversely correlated with EGFR expression in the tamoxifen resistant group only. We conclude that IGF-1 ligand and ERα expression in breast carcinomas can be measured to predict tamoxifen resistance. Measuring ERα expression using RT-PCR may be more sensitive than immunohistochemistry in determining anti-oestrogen sensitivity.