Insulin-like growth factor binding proteins 1 and 3 and breast cancer outcomes.
The IGF family of growth factors is believed to play a role in the development and progression of breast cancer. We recently identified an adverse prognostic effect of insulin in breast cancer; we now report prognostic effects of circulating IGFBP's 1 and 3. 512 women with T1-3, N0-1, M0 breast cancer provided fasting blood which was analysed for IGFBP's I and 3. Information on body size, diet and traditional prognostic factors and treatment was obtained; women were followed for recurrence and death. IGFBP-1 levels correlated inversely with insulin levels (Spearman r = -0.60, p < 0.0001), reflecting known inhibition of IGFBP-1 gene expression by insulin. Insulin explained 36% of the variance in IGFBP-1 levels. IGFBP-1 levels were also correlated with obesity and diet. Levels of IGFBP-1 significantly predicted distant recurrence and death, hazard ratio (95% CI) for lower versus upper quartile 2.08 (1.20-3.61) and 3.0 (1.45-6.21), respectively. These effects persisted after adjustment for tumor-related variables and treatment but were not independent of insulin levels. High levels of IGFBP-3 predicted distant recurrence (hazard ratio upper v.s. lower quartile 1.8, 95% CI 1.1-3.0) but not death (hazard ratio 1.0, 95% CI 0.5-1.9). The effect on distant recurrence was restricted to postmenopausal women (hazard ratio 3.8, 95% CI 1.6-9.0) and to those with estrogen receptor positive tumors (p = 0.002). Prognostic effects of IGFBP-1 appear related to the known effect of insulin on IGFBP-1 gene expression. The adverse effect of IGFBP-3 on distant recurrence in postmenopausal women with estrogen receptor positive breast cancer should be further investigated.
Goodwin
Pamela J
PJ
Department of Medicine, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada. pgoodwin@mtsinai.on.ca
Ennis
Marguerite
M
Pritchard
Kathleen I
KI
Trudeau
Maureen E
ME
Koo
Jarley
J
Hartwick
Warren
W
Hoffma
Barry
B
Hood
Nicky
N
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000473:pathology*; D004032:Diet; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000032:analysis* / Q000096:biosynthesis; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis* / Q000096:biosynthesis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D017698:Postmenopause; D011237:Predictive Value of Tests; D011379:Prognosis; D011960:Receptors, Estrogen; D013534:Survival
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D011960:Receptors, Estrogen