Research article

Sex steroids, growth factors and mammographic density: a cross-sectional study of UK postmenopausal Caucasian and Afro-Caribbean women

Valerie A McCormack^1,2 , Mitch Dowsett³ , Elizabeth Folkerd³ , Nichola Johnson⁴ , Claire Palles⁴ , Ben Coupland⁴ , Jeff M Holly⁵ , Sarah J Vinnicombe⁶ , Nicholas M Perry⁶ and Isabel dos Santos Silva¹

¹  Cancer Research UK Epidemiology and Genetics Group, Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK

²  International Agency for Research on Cancer, 150 cours Albert Thomas, Lyon 69008, France

³  The Academic Department of Biochemistry, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK

⁴  Cancer Research UK Epidemiology and Genetics Group, Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK

⁵  University Department of Clinical Science at North Bristol, Southmead Hospital, Southmead Road, Westbury-on-Trym, Bristol BS10 5NB, UK

⁶  Breast Assessment Centre, St Bartholomew's Hospital, Barts and The London NHS Trust, West Smithfield, London EC1A 7BE, UK

author email corresponding author email

Breast Cancer Research 2009, 11:R38doi:10.1186/bcr2325

Published:	22 June 2009

Abstract

Introduction

Sex steroids, insulin-like growth factors (IGFs) and prolactin are breast cancer risk factors but whether their effects are mediated through mammographic density, one of the strongest risk factors for breast cancer, is unknown. If such a hormonal basis of mammographic density exists, hormones may underlie ethnic differences in both mammographic density and breast cancer incidence rates.

Methods

In a cross-sectional study of 270 postmenopausal Caucasian and Afro-Caribbean women attending a population-based breast screening service in London, UK, we investigated whether plasma biomarkers (oestradiol, oestrone, sex hormone binding globulin (SHBG), testosterone, prolactin, leptin, IGF-I, IGF-II and IGF binding protein 3 (IGFBP3)) were related to and explained ethnic differences in mammographic percent density, dense area and nondense area, measured in Cumulus using the threshold method.

Results

Mean levels of oestrogens, leptin and IGF-I:IGFBP3 were higher whereas SHBG and IGF-II:IGFBP3 were lower in Afro-Caribbean women compared with Caucasian women after adjustment for higher mean body mass index (BMI) in the former group (by 3.2 kg/m² (95% confidence interval (CI): 1.8, 4.5)). Age-adjusted percent density was lower in Afro-Caribbean compared with Caucasian women by 5.4% (absolute difference), but was attenuated to 2.5% (95% CI: -0.2, 5.1) upon BMI adjustment. Despite ethnic differences in biomarkers and in percent density, strong ethnic-age-adjusted inverse associations of oestradiol, leptin and testosterone with percent density were completely attenuated upon adjustment for BMI. There were no associations of IGF-I, IGF-II or IGFBP3 with percent density or dense area. We found weak evidence that a twofold increase in prolactin and oestrone levels were associated, respectively, with an increase (by 1.7% (95% CI: -0.3, 3.7)) and a decrease (by 2.0% (95% CI: 0, 4.1)) in density after adjustment for BMI.

Conclusions

These findings suggest that sex hormone and IGF levels are not associated with BMI-adjusted percent mammographic density in cross-sectional analyses of postmenopausal women and thus do not explain ethnic differences in density. Mammographic density may still, however, be influenced by much higher premenopausal hormone levels.