IGF status is altered by tamoxifen in patients with breast cancer

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Abstract
Aims—An increased concentration of insulin-like growth factor 1 (IGF-1) is an independent risk factor for premenopausal breast cancer. Tamoxifen is thought initially to reduce concentrations of IGF-1 and increase concentrations of the IGF binding proteins. The aim of this study was to compare concentrations of IGF-1, IGF binding protein 1 (IGF-BP1), and IGF-BP3 in patients with breast cancer (n = 14) with those seen in control subjects (n = 23) and to assess the effect of tamoxifen on IGF status in these patients. Methods—Non-fasting blood samples were collected from patients with breast cancer before surgery and after nine, 18, and 27 months of tamoxifen treatment. The baseline concentrations were compared with those of age and sex matched healthy control subjects. Results—IGF-1, IGF-BP3, and IGF-BP1 concentrations were not significantly different in cases and controls. Tamoxifen treatment significantly increased IGF-BP1 after 18 and 27 months (baseline: mean, 21.6 ng/ml; SD, 16.6; 18 months: mean, 52.0 ng/ml; SD, 41.8; p = 0.019; 27 months: mean, 40.7 ng/ml; SD, 24.9; p = 0.043) and IGF-BP3 after nine, 18, and 27 months (baseline: mean, 3119 ng/ml; SD, 507; nine months: mean, 3673 ng/ml; SD, 476; p = 0.004; 18 months: mean, 3445 ng/ml; SD, 634; p = 0.034; 27 months: 3409 ng/ml; SD, 501; p = 0.043) when compared with baseline values. IGF-1 was not altered significantly from baseline at any time point. However, the IGF-1 to IGF-BP3 ratio was significantly decreased at both nine and 18 months (baseline: mean, 0.058; SD, 0.014; nine months: mean, 0.039; SD, 0.008; p = 0.033; 18 months: mean, 0.044; SD, 0.012; p = 0.01). This ratio was not significantly different from baseline at 27 months (mean, 0.054; SD, 0.01; p = 0.08). Conclusions—Tamoxifen increases IGF-BP3 and IGF-BP1 concentrations. It also decreases the IGF-1 to IGF-BP3 ratio but this effect may be limited after long term use. Longer follow up, with larger numbers of patients, should determine when, and for how long, tamoxifen can reduce circulating IGF-1.