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Mammographic density and breast cancer risk: the role of the fat surrounding the fibroglandular tissue

Mariëtte Lokate1, Petra HM Peeters14, Linda M Peelen1, Gerco Haars2, Wouter B Veldhuis3 and Carla H van Gils1*

Author Affiliations

1 Julius Center for Health Sciences and Primary Care, Str. 6.131, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands

2 Julius Clinical Research, J.F. Kennedylaan 101 III,3981 GB Bunnik, The Netherlands

3 Department of Radiology, E01.132, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands

4 Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St. Mary's Campus, Norfolk Place W2 1PG London, UK

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Breast Cancer Research 2011, 13:R103  doi:10.1186/bcr3044

See related editorial by Shepherd and Kerlikowske,

Published: 26 October 2011



Both the percent of mammographic density and absolute dense (fibroglandular) area are strong breast cancer risk factors. The role of non-dense (fat) breast tissue is not often investigated, but we hypothesize that this also influences risk. In this study we investigated the independent effects of dense and fat tissue, as well as their combined effect on postmenopausal breast cancer risk.


We performed a nested case-control study within the EPIC-NL cohort (358 postmenopausal breast cancer cases and 859 postmenopausal controls). We used multivariate logistic regression analyses to estimate breast cancer odds ratios adjusted for body mass index and other breast cancer risk factors.


Large areas of dense (upper (Q5) vs lower quintile (Q1): OR 2.8 95% CI 1.7 to 4.8) and fat tissue (Q5 vs Q1: OR 2.4; 95% CI 1.3 to 4.2) were independently associated with higher breast cancer risk. The combined measure showed that the highest risk was found in women with both a large (above median) area of dense and fat tissue.


Fibroglandular and breast fat tissue have independent effects on breast cancer risk. The results indicate that the non-dense tissue, which represents the local breast fat, increases risk, even independent of body mass index (BMI). When studying dense breast tissue in relation to breast cancer risk, adjustment for non-dense tissue seems to change risk estimates to a larger extent than adjustment for BMI. This indicates that adjustment for non-dense tissue should be considered when studying associations between dense areas and breast cancer risk.