Effects of tamoxifen on insulin-like growth factors, IGF binding proteins and IGFBP-3 proteolysis in breast cancer patients.
BACKGROUND
Recently an association between increased serum insulin-like growth factor I (IGF-I) levels and the development of breast cancer was demonstrated. Tamoxifen used in the postoperative treatment of breast cancer patients may exert significant effects on the IGF-I system.


METHODS
To examine the effect of Tamoxifen treatment (20 mg/day) on changes in the IGF-I axis in 11 breast cancer patients before and after 4 months of Tamoxifen treatment and compared to 8 healthy subjects. IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-6 were examined by specific assays. IGFBPs were examined by Western ligand blotting and IGFBP-3 proteolytic activity by specific protease assay.


RESULTS
Serum IGF-I was decreased before (63%) and increased during Tamoxifen treatment (60%). Total IGFBP-3 levels measured by IRMA were unchanged, however, intact IGFBP-3 measured by WLB was decreased (58%) before and increased (67%) during Tamoxifen treatment. IGFBP-3 proteolysis was increased before and reduced during treatment. IGFBP-4 and IGFBP-6 were decreased before and increased during Tamoxifen treatment.


CONCLUSIONS
Significant changes in the IGF system were demonstrated before and during Tamoxifen treatment and may in part be involved in the effects of Tamoxifen treatment in breast cancer patients.
Grønbaek
Henning
H
Institute of Experimental Clinical Research, Aarhus Kommunehospital, Aarhus University Hospital, Aarhus C, Denmark. henning.gronbaek@dadlnet.dk
Tanos
Vasilios
V
Meirow
Dror
D
Peretz
Tamar
T
Raz
Itamar
I
Flyvbjerg
Allan
A
D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy*; D016022:Case-Control Studies; D010450:Endopeptidases / Q000378:metabolism; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D013002:Somatomedins / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*
D020847:Estrogen Receptor Modulators; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D013629:Tamoxifen; D010450:Endopeptidases; C080473:insulin-like growth factor binding protein-3 protease