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

Abstract

IntroductionBoth 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.MethodsWe 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.ResultsLarge 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.ConclusionsFibroglandular 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.

Anthropometric factors, adult weight gain, and mammographic features

“…In a recent meta-analysis, Pettersson et al [7] found a strong inverse association between absolute non-dense area and breast cancer risk, independent of dense area. This observation is supported by other studies [10,11], although not all [12,13].…”

“…Stone et al [12] also found an inverse association which was lost after adjustment for dense area. On the other hand, Lokate et al [13] found a positive association between non-dense area and breast cancer risk. These discrepant results have been thought to be due to the difference in the mammogram view used for the evaluation of non-dense area.…”

Insulin-like growth factor-1, growth hormone, and daily cycling estrogen are associated with mammographic density in premenopausal women

“…Thus, estrogen and growth factors may influence not only the dense area, but the stroma and the surrounding adipose tissue. Importantly, others have observed that fibroglandular and fat tissue may have independent effects on breast cancer development [40].…”

Breast Density and Breast Cancer Risk: Understanding of Biology and Risk

“…Higher absolute nondense area (i.e., higher amounts of breast adipose tissue) has been linked with both increased [8] and decreased [9] breast cancer risk. In a recent meta-analysis including data from 13 case-control studies, absolute nondense area was inversely associated with breast cancer risk (odds ratio [OR] for a one standard deviation increment in absolute nondense area among postmenopausal women=0.85, 95 % CI 0.75-0.96) [10]; however, because of between-study heterogeneity, it remains unclear if the inverse association between the absolute nondense area and breast cancer risk is independent of the absolute dense area.…”