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This Article Accepted manuscript (PDF) All Versions of this Article: EJE-08-0154v1 159/5/595    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Espelund, U. Articles by Flyvbjerg, A. PubMed PubMed Citation Articles by Espelund, U. Articles by Flyvbjerg, A.

Elevated free IGF-II levels in localized, early-stage breast cancer in women

U Espelund, Medical Research Laboratories, Clinical Institute and Dept. M (Diabetes and Endocrinology), Aarhus University Hospital, Aarhus, Denmark
S Cold, R (Oncology), Odense University Hospital, Odense, Denmark
J Frystyk, Medical Research Laboratories, Clinical Institute and Dept. M (Diabetes and Endocrinology), Aarhus University Hospital, Aarhus, Denmark
H Orskov, Medical Research Laboratories, Clinical Institute and Dept. M (Diabetes and Endocrinology), Aarhus University Hospital, Aarhus, Denmark
A Flyvbjerg, Medical Research Laboratories, Clinical Institute and Dept. M (Diabetes and Endocrinology), Aarhus University Hospital, Aarhus, Denmark

Correspondence: Ulrick Espelund, Email: uespelund{at}hotmail.com

Abstract

Objective. Epidemiological studies imply an association between circulating insulin-like growth factor I (IGF-I) and breast cancer, whereas the role of IGF-II, which also acts on the IGF-I receptor, is less settled. This study investigates the association between IGF-II and breast cancer in patients with localized disease.

Design. The participants were women with well-characterized, early stage, localized breast cancer (n=43) and matched healthy women (n=38), from whom fasting serum levels of IGF-related peptides were measured.

Results. In patients, mean free IGF-II was increased (+57%, P<0.001) in spite of reduced total IGF-II levels (-12%, P=0.003) as compared to controls. Similar changes were seen in free IGF-I (+28%, P=0.004) and total IGF-I (-16% P=NS). Pro-IGF-II and IGF binding protein 1 (IGFBP-1) were unchanged. IGFBP-2 was reduced by 22% in the patients (P=0.004). Patients showed reduced IGFBP-3 protease activity and accordingly increased levels of intact IGFBP-3, whereas total IGFBP-3 was unchanged.

Conclusion. Women with localized, early-stage breast cancer show elevated circulating free IGF-I and -II, reduced total IGF-II and alterations in IGFBPs. The changes observed despite minimal cancer disease suggest a role for the circulating IGF-system in the progression of breast cancer in women.