Insulin-like growth factor i and risk of breast cancer by age and hormone receptor status - A prospective study within the EPIC cohort

Rudolf Kaaks, Theron Johnson, Kaja Tikk, Disorn Sookthai, Anne Tjønneland, Nina Roswall, Kim Overvad, Françoise Clavel-Chapelon, Marie Christine Boutron-Ruault, Laure Dossus, Sabina Rinaldi, Isabelle Romieu, Heiner Boeing, Madlen Schütze, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Domenico Palli, Sara Grioni, Rosario TuminoCarlotta Sacerdote, Salvatore Panico, Genevieve Buckland, Marcial Argüelles, María José Sánchez, Pilar Amiano, Maria Dolores Chirlaque, Eva Ardanaz, H. Bas Bueno-De-Mesquita, Carla H. Van Gils, Petra H. Peeters, Anne Andersson, Malin Sund, Elisabete Weiderpass, Inger Torhild Gram, Eiliv Lund, Kay Tee Khaw, Nick Wareham, Timothy J. Key, Ruth C. Travis, Melissa A. Merritt, Marc J. Gunter, Elio Riboli, Annekatrin Lukanova

Research output: Contribution to journalArticlepeer-review


Experimental evidence shows cross-talk in mammary cells between estrogen, insulin-like growth factor I (IGF-I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF-I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF-I levels may be related more to the risk of ER-positive than ER-negative breast cancer. Using a case-control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF-I levels with the risk of estrogen and progesterone receptor-positive and -negative breast tumors. IGF-I levels were positively associated with the risk of ER+ breast tumors overall (pre- and postmenopausal women combined, odds ratio (OR)Q4-Q1 = 1.41 [95% confidence interval (CI) 1.01-1.98] for the highest vs. lowest quartile; OR = 1.17 [95% CI 1.04-1.33] per 1-standard deviation (SD) increase in IGF-I, ptrend = 0.01) and among women who were diagnosed with breast cancer at 50 years or older (ORQ3-Q1 = 1.38 [95% CI 1.01-1.89]; OR = 1.19 [95% CI 1.04-1.36] per 1-SD increase in IGF-I, ptrend = 0.01) but not with receptor-positive disease diagnosed at an earlier age. No statistically significant associations were observed for ER- breast tumors overall and by age at diagnosis. Tests for heterogeneity by receptor status of the tumor were not statistically significant, except for women diagnosed with breast cancer at 50 years or older (phet = 0.03 for ER+/PR+ vs. ER-/PR- disease). Our data add to a global body of evidence indicating that higher circulating IGF-I levels may increase risk specifically of receptor-positive, but not receptor-negative, breast cancer diagnosed at 50 years or older. What's new Both estrogen and insulin-like growth factor (IGF-I) promote breast cancer formation, and evidence suggests the two may work together. Some breast tumors express estrogen receptor, others don't. Does the presence of estrogen receptor allow IGF-I to stimulate tumor formation To address this question, the authors compared women's IGF-I levels before diagnosis with their risk of developing breast cancer, with or without estrogen receptor. They found a direct relationship between IGF levels and risk of ER-positive breast tumors diagnosed after age 50. They found no association with ER-positive tumors diagnosed at an earlier age, nor with ER-negative tumors.

Original languageEnglish
Pages (from-to)2683-2690
Number of pages8
JournalInternational Journal of Cancer
Issue number11
Publication statusPublished - Jun 1 2014


  • breast cancer
  • estrogen receptor
  • European Prospective Investigation into Cancer and Nutrition
  • insulin-like growth factor I
  • prospective cohort

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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