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: 5.49). 12/2011; 13(5):R103. DOI: 10.1186/bcr3044
Source: PubMed


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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    • "Within the breast cancer literature, numerous studies have demonstrated that greater dense area and percent density are strong risk factors for breast cancer [12-14]. Nondense area may also confer risks for breast cancer independent of breast density although the direction of the association is unclear [15,16]. Although the reasons underlying these associations are incompletely understood, mammographic density has emerged as an important factor for the prediction of breast cancer risk [17]. "
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    ABSTRACT: Breast fibroglandular (dense) tissue is a risk factor for breast cancer. Beyond breast cancer, little is known regarding the prognostic significance of mammographic features. We evaluated relationships between nondense (fatty) breast area and dense area with all-cause mortality in 4,245 initially healthy women from the Breast Cancer Detection Demonstration Project; 1,361 died during a mean follow-up of 28.2 years. Dense area and total breast area were assessed using planimeter measurements from screening mammograms. Percent density reflects dense area relative to breast area and nondense area was calculated as the difference between total breast area and dense area. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression. In age-adjusted models, greater nondense and total breast area were associated with increased risk of death (HR 1.17, 95% CI 1.10-1.24 and HR 1.13, 95% CI 1.06-1.19, per SD difference) while greater dense area and percent density were associated with lower risk of death (HR 0.91, 95% CI 0.86-0.95 and HR 0.87, 95% CI 0.83-0.92, per SD difference). Associations were not attenuated with adjustment for race, education, mammogram type (x-ray or xerogram), smoking status, diabetes and heart disease. With additional adjustment for body mass index, associations were diminished for all features but remained statistically significant for dense area (HR 0.94, 95% CI 0.89-0.99, per SD difference) and percent density (HR 0.93, 95% CI 0.87-0.98, per SD difference). These data indicate that dense area and percent density may relate to survival in healthy women and suggest the potential utility of mammograms beyond prediction of breast cancer risk.
    Full-text · Article · Oct 2013 · PLoS ONE
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    • "However, the fatty tissue of the breast is an important contributor of local oestrogens (Thijssen, 2004) and could thus influence tumour subtype. Hence, we also carried out analyses adjusting for the non-dense area, based on results from a study by Lokate et al (2011), showing that AD adjusted for the non-dense area was an even better model for breast cancer risk prediction than both PD and AD adjusted for BMI. Adjustment for the non-dense area did not, however, change the interpretation of our results (data not shown). "
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    ABSTRACT: Gene expression profiling has led to a subclassification of breast cancers independent of established clinical parameters, such as the Sorlie-Perou subtypes. Mammographic density (MD) is one of the strongest risk factors for breast cancer, but it is unknown if MD is associated with molecular subtypes of this carcinoma. We investigated whether MD was associated with breast cancer subtypes in 110 women with breast cancer, operated in Stockholm, Sweden, during 1994 to 1996. Subtypes were defined using expression data from HGU133A+B chips. The MD of the unaffected breast was measured using the Cumulus software. We used multinomial logistic models to investigate the relationship between MD and Sorlie-Perou subtypes. Although the distribution of molecular subtypes differed in women with high vs low MD, this was statistically non-significant (P=0.249), and further analyses revealed no association between the MD and Sorlie-Perou subtypes as a whole, nor with individual subtypes. These findings suggest that although MD is one of the strongest risk factors for breast cancer, it does not seem to be differentially associated with breast cancer molecular subtypes. However, larger studies with more comprehensive covariate information are needed to confirm these results.
    Full-text · Article · May 2012 · British Journal of Cancer
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    ABSTRACT: Few studies have investigated the association of non-dense area or fatty breasts in conjunction with breast density and breast cancer risk. Two articles in a recent issue of Breast Cancer Research investigate the role of absolute non-dense breast area measured on mammograms and find conflicting results: one article finds that non-dense breast area has a modest positive association with breast cancer risk, whereas the other finds that non-dense breast area has a strong protective effect to reduce breast cancer risk. Understanding the interplay of body mass index, menopause status, and measurement of non-dense breast area would help to clarify the contribution of non-dense breast area to breast cancer risk.
    Full-text · Article · Jan 2012 · Breast cancer research: BCR
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