Serum IGF-1, IGFBP-3 levels and circulating tumor cells (CTCs) in early breast cancer patients.
OBJECTIVE
Insulin-like growth factor (IGF)-axis is involved in human oncogenesis and metastasis development for various solid tumors including breast cancer. Aim of this study was to assess the association between IGF-1, IGF-binding protein-3 (IGFBP-3) serum levels and the presence of circulating tumor cells (CTCs) in the peripheral blood of women diagnosed with early breast cancer (EBC), before and after adjuvant chemotherapy.


DESIGN
171 patients with early-stage breast adenocarcinomas were retrospectively evaluated. Immunoradiometric (IRMA) assays were employed for the in-vitro determination of IGF-1 and IGFBP-3 serum levels in blood samples collected after surgical treatment and before initiation of adjuvant chemotherapy. CTCs' presence was assessed through detection of cytokeratin-19 (CK-19) mRNA transcripts using quantitative real time reverse transcription polymerase chain reaction (RT-PCR). IGF-1, IGFBP-3 serum levels were correlated with CTCs' presence before and after adjuvant chemotherapy as well as with tumor characteristics including tumor size, axillary lymph node status, oestrogen (ER)/progestorene (PR) and human epidermural growth factor receptor 2 (HER2) receptor status. Log-rank test was applied to investigate possible association between IGF-1, IGFBP-3 serum levels and disease-free interval (DFI) and overall survival (OS).


RESULTS
Before initiation of adjuvant therapy IGF-1, IGFBP-3 serum levels were moderately associated (Spearman's rho=0.361, p<0.001) with each other, while presenting significant differences across age groups (all p values<0.05). IGF-1 serum levels did not correlate with the presence of CTCs before initiation (p=0.558) or after completion (p=0.474) of adjuvant chemotherapy. Similarly, IGFBP-3 serum levels did not show significant association with detectable CTCs either before (p=0.487) or after (p=0.134) completion of adjuvant chemotherapy. There was no statistically significant association between the clinical outcome of patients in terms of DFI, OS and IGF-1(DFI: p=0.499; OS: p=0.220) or IGFBP-3 (DFI: p=0.900; OS: p=0.406) serum levels.


CONCLUSIONS
IGF-1 and IGFBP-3 serum levels before initiation of adjuvant chemotherapy are not indicative of CTCs' presence in the blood and do not correlate with clinical outcome of women with early-stage breast cancer.
['Papadakis|Georgios Z|GZ|', 'Mavroudis|Dimitrios|D|', 'Georgoulias|Vasilios|V|', 'Souglakos|John|J|', 'Alegakis|Athanasios K|AK|', 'Samonis|George|G|', 'Bagci|Ulas|U|', 'Makrigiannakis|Antonis|A|', 'Zoras|Odysseas|O|']
D000230:Adenocarcinoma D000328:Adult D000368:Aged D000369:Aged, 80 and over D001943:Breast Neoplasms D017024:Chemotherapy, Adjuvant D005260:Female D006801:Humans D018972:Insulin-Like Growth Factor Binding Protein 3 D007334:Insulin-Like Growth Factor I D008875:Middle Aged D009360:Neoplastic Cells, Circulating D011379:Prognosis D012189:Retrospective Studies
Circulating tumor cells (CTCs) IGF-binding protein-3 (IGFBP-3) Early breast cancer (EBC) Biomarkers Insulin-like growth factor-1 (IGF-1) Prognosis