Increase in Serum Total IGF-I and Maintenance of Free IGF-I Following Intentional Weight Loss in Pre-menopausal Women at Increased Risk of Breast Cancer

Harvie M.*, 1, Renehan A. G.2, Frystyk J.3, Flyvbjerg A.3, Mercer T.4, Malik R.5, Adams J.5, Cuzick J.6, Howell A.1
1 Genesis Prevention Centre, University Hospital of South Manchester NHS Foundation Trust, Manchester, UK
2 School of Cancer, Enabling Sciences and Technology, University of Manchester, UK
3 The Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Aarhus, Denmark
4 Department of Physiotherapy, Queen Margaret University, Edinburgh, UK
5 Department of Clinical Radiology, University of Manchester, UK
6 Cancer Research UK Departments of Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine London, UK

© 2010 Harvie et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Genesis Prevention Centre, University Hospital of South Manchester NHS Foundation Trust, Manchester, M23 9LT, UK; Tel: +44 (0) 161 291 4410; Fax: +44 (0) 161 291 4412; E-mail:


Intentional weight loss may reduce breast cancer risk through lowering levels of circulating free IGF-I but few studies have measured this longitudinally. We determined the effect of weight loss (≥5% body weight) over 12 months, using an energy restriction and exercise programme, on an expanded panel of IGF-related peptides amongst 23 weight losing and 46 weight stable or gaining pre-menopausal women at increased risk of breast cancer, BMI (mean ± SD) 29.2 ± 6.2 kg/m2. Fasting measures of total and free IGF-I (ultra-filtration), and IGFBP-1, -2 and -3, body weight, body fat (DXA), intra-abdominal fat (MRI) were assessed at 6 and 12 months.

After 12 months, women who lost ≥5% of body weight had a significant increase in serum total IGF-I; mean (95% CI difference) 17 (2.3 to 34.0) μg/l, P < 0.05, and IGFBP-2; mean (95% CI ratio) 1.24 (1.06 to 1.46) P < 0.001, compared to weight stable/gaining women. Serum IGFBP-1 tended to increase in weight losers compared to the weight stable/gaining women; mean (95% CI ratio) 1.19 (0.97 to 1.45) P=0.09, whereas IGFBP-3 remained unchanged; mean (95% CI ratio) 1.02 (0.94 to 1.20] P=0.99. Weight loss did not significantly alter serum levels of free IGF-I; mean difference 0.1 (-0.1 to 3.4) μg/l, P=0.21.

Increased serum total IGF-I levels, and maintenance of free IGF-I despite increased concentrations of serum IGFBP-1 and -2 with weight loss, does not suggest intentional weight loss with diet and exercise mediates reduced risk through the circulating IGF-axis.

Keywords: Intentional weight loss, IGF-I, free IGF-I, IGFBP-1, IGFBP-2, breast cancer.