Influence of droloxifene on plasma levels of insulin-like growth factor (IGF)-I, Pro-IGF-IIE, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-3 in breast cancer patients.
The influence of the novel anti-estrogen droloxifene on the insulin-like growth factor (IGF) system in plasma was studied in two groups of breast cancer patients receiving droloxifene 40 mg o.d. (group 1, n = 6) or 100 mg o.d. (group 2, n = 7). Fasting blood samples were obtained from all patients before treatment and after 3 months (group 1) or 6 months (group 2) on droloxifene treatment, except for two patients in group 2 from whom the second sample was obtained following 2 months on treatment when the drug was to be terminated due to progressive disease. Insulin-like growth factor (IGF)-I, insulin-like growth factor binding protein (IGFBP)-1, IGFBP-3 and pro-IGF-IIE (IGF-IIE) were measured by radioimmunoassay. In patients in group 1, plasma lGF-I levels decreased by a mean value of 20% (P < 0.05) on treatment with droloxifene, while IGFBP-1 increased by a mean value of 45% (P > 0.1). In group 2 we observed a 42% decrease in IGF-I during treatment (P < 0.025), while the level of IGFBP-1 increased by a mean value of 70% (P < 0.025). No significant effect on IGF-IIE or IGFBP-3 was noted in any of the groups. The change in plasma lGF-I and IGFBP-1 observed during treatment with droloxifene resembles what is found in patients treated with tamoxifen. As IGF-I is a potent mitogen for breast cancer cells in vitro, a decrease in the plasma level of this growth factor with an increase in the concentration of IGFBP-1 may contribute to the anti-tumour effects of droloxifene.
Helle
S I
SI
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
Anker
G B
GB
Tally
M
M
Hall
K
K
Lønning
P E
PE
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008875:Middle Aged; D011498:Protein Precursors / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D011498:Protein Precursors; D013002:Somatomedins; C066038:proinsulin-like growth factor II; D013629:Tamoxifen; C038345:droloxifene; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II