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

Julius Center for Health Sciences and Primary Care, Str. 6,131, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
Breast cancer research: BCR (Impact Factor: 5.87). 12/2011; 13(5):R103. DOI: 10.1186/bcr3044
Source: PubMed

ABSTRACT 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.

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    ABSTRACT: Mammographic density represents epithelial and stromal proliferation, while insulin-like growth factor (IGF)-1, insulin-like growth factor-binding protein-3, growth hormone (GH), and estrogen may influence cellular proliferation. However, whether these growth factors independently, or in combination with estrogen, influence mammographic density in premenopausal women remains unclear. Growth factors were assessed in 202 ovulating premenopausal women participating in the Energy Balance and Breast Cancer Aspects-I study. Estrogen was assessed in serum, and daily in saliva, throughout a menstrual cycle. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms (days 7-12 of the menstrual cycle). Associations between growth factors, estrogen, and mammographic density were studied in regression models. Women with a mean age of 30.7 years had a mean percent mammographic density of 29.8 %. Among women in the strata (above median split) of IGF-1 (>25 nmol/l) or GH (>0.80 mlU/l), we observed that an increase in salivary 17β-estradiol was associated with a higher odds for having higher percent mammographic density (>28.5 %). The odds ratios (ORs) per standard deviation increase in 17β-estradiol were 1.81 [95 % confidence interval (CI) 1.08-3.03] in the high IGF-1 stratum and 2.08 (95 % CI 1.10-3.94) in the high GH stratum. Furthermore, women in these strata of growth factors (above median) who had an overall average 17β-estradiol above median (>16.8 pmol/l) had higher ORs for having higher percent mammographic density (>28.5 %): IGF-1 4.13 (95 % CI 1.33-12.83) and GH 4.17 (95 % CI 1.41-12.28). Growth factors, in combination with cycling estrogen, were associated with percent mammographic density, and may be of potential clinical relevance.
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