Background: Components of the insulin-like growth factor system are deregulated and IGFIR overexpression is commonly observed in BC, however the expression of the receptor in CTCs of patients with BC has not been studied.

Methods: IGFIR expression was assessed in CTCs from 65 patients with early and 101 with metastatic breast cancer before the start of adjuvant and first-line chemotherapy, respectively. Peripheral blood mononuclear cells’ (PBMCs) cytospins were stained with a monoclonal A45-B/B3 anti-cytokeratin (CK) antibody and IGFIR β-subunit anti-rabbit antibody. IGFIR(+)CK(+) CTCs were detected using immunofluorescent microscopy (Ariol system). Phosphorylated IGFIR was also evaluated after staining with phospho-IGFIR-β (Tyr1131)/Insulin Receptor-β (Tyr1146) antibody.

Results: CK(+) CTCs were detected in 23 (35.3%) patients with early and 48.5% with metastatic BC. IGFIR(+) CTCs were identified in all (100%) patients with early and in 38 (78%) out of 49 patients with metastatic BC (p=0.014). Eighteen (78%) out of 23 patients with early disease had exclusively IGFIR(+) CTCs and 5(22%) had both IGFIR(+) and IGFIR(−) CTCs. There were no patients in whom exclusively IGFIR(−) CTCs were identified. The respective values in patients with metastatic disease were 19 (39%), 19 (39%) and 11 (22%) (p=0.004, compared to early disease). The median percentage of the expression of IGFIR(+) and IGFIR(−) CTCs per patient was 100% (range 25–100) and 0% (range 0–75), in early and 68% (range, 0–100) and 32% (range 0–100), in metastatic disease, respectively (p=0.003). A total of 222 and 386 CTCs were detected in patients with early and metastatic disease, respectively. IGFIR expression was observed in 84% and 64% of all detected CTCs in adjuvant and metastatic patients, respectively (p<0.001). Phosphorylated IGFIR has been evaluated in PBMCs’ cytospins from 6 patients with adjuvant and 6 with metastatic disease. Interestingly, among 18 CTCs detected in early BC, all expressed phosphorylated IGFIR, whereas, among 34 CTCs identified in metastatic patients, none expressed the phosphorylated form of the receptor. The evaluation of phosphorylated IGFIR is ongoing and updated results will be presented.

Conclusions: IGFIR expression is commonly observed in CTCs of patients with BC. IGFIR expression is detected in a higher proportion of patients and in a higher proportion of the total number of CTCs identified in early compared to metastatic disease. The above observations suggest that metastatic progression is associated with loss or downregulation of IGFIR expression in breast cancer.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-15.

2011