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¹ International Agency for Research on Cancer (IARC-WHO), 150 Cours Albert Thomas, 69372 Lyon, Cédex 08, France
² Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands
³ National Cancer Institute, Milan, Italy
⁴ The Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark
⁵ Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark
⁶ INSERM, Institut Gustave Roussy, Villejuif, France
⁷ Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany
⁸ German Institute of Human Nutrition, Department of Epidemiology, Potsdam-Rehbrücke, Germany
⁹ University of Athens Medical School, Athens, Greece
¹⁰ Molecular and Nutritional Epidemiology Unit, CSPO, Scientific Institute of Tuscany, Florence, Italy
¹¹ Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy
¹² Cancer Registry, Azienda Ospedaliera ‘Civile M P Arezzo’, Ragusa, Italy
¹³ CPO-Piemonte, Torino, Italy
¹⁴ Center for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
¹⁵ Department of Epidemiology, Catalan Institute of Oncology, Barcelona, Spain
¹⁶ Epidemiology Department, Murcia Health Council, Murcia, Spain
¹⁷ Public Health Institute of Navarra, Pamplona, Spain
¹⁸ Public Health Division of Gipuzkoa, Health Department of the Basque Country, Donostia-San Sebastian, Spain
¹⁹ Public Health and Health Planning Directorate, Asturias, Spain
²⁰ MRC Centre for Nutrition in Cancer Prevention and Survival, University of Cambridge, Department of Public Health and Primary Care, Cambridge, United Kingdom
²¹ Clinical Gerontology Unit, Addenbrooke’s Hospital, Cambridge, United Kingdom
²² Epidemiology Unit, Cancer Research UK, University of Oxford, Oxford, United Kingdom
²³ New York University School of Medicine, New York, USA
²⁴ Imperial College, London, United Kingdom

(Requests for offprints should be addressed to R Kaaks; Email: kaaks{at}iarc.fr)

Blood concentrations of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) have recently been associated with breast cancer risk, notably in women who developed breast cancer at a young age. Prospective studies published so far, however, were relatively small and odds ratio (OR) estimates imprecise. We present the results of a large prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition on total IGF-I, IGFBP-3 and breast cancer risk including 1081 incident cases of invasive breast cancer and 2098 matched control subjects. Increasing IGF-I and IGFBP-3 concentrations were associated with a significant increase in breast cancer risk in women who developed breast cancer after 50 years of age (highest vs lowest quintile OR 1.38 (95% confidence interval (CI) 1.02–1.86), P = 0.01, and 1.44 (95% CI 1.04–1.98), P = 0.01, respectively), but no relationship was observed in younger women (OR = 1.03 (95% CI 0.60–1.77), P = 0.81 for IGF-I, and OR = 0.92 (95% CI 0.50–1.70), P = 0.69 for IGFBP-3). There was, however, significant heterogeneity in the relationship of breast cancer with serum IGF-I and IGFBP-3 levels depending on the time interval between blood donation and tumor diagnosis. A reduction in breast cancer risk with increasing IGF-I concentrations was observed in cases with a diagnosis of cancer less than 2 years after blood donation, (OR = 0.76 (95% CI 0.57–1.03)), while an increase in risk was observed for women with a later diagnosis (above or equal to two years after blood collection, OR = 1.51 (95% CI 1.19–1.91)). A similar pattern was observed for IGFBP-3. This study confirms previous findings for an association of serum IGF-I and IGFBP-3 concentrations with breast cancer risk, particularly for women with a later diagnosis of cancer, but it does not support the hypothesis of an involvement of IGF-I in younger women.

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