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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.    Methods  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.    Results  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.    Conclusions  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.

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