Abstract
BACKGROUND: Mammographic percentage density is an established and important risk factor for breast cancer. In this paper, we investigate the role of the spatial organisation of (dense vs. fatty) regions of the breast defined from mammographic images in terms of breast cancer risk. METHODS: We present a novel approach that provides a thorough description of the spatial organisation of different types of tissue in the breast. Each mammogram is first segmented into four regions (fatty, semi-fatty, semi-dense and dense tissue). The spatial relations between each pair of regions is described using so-called forces histograms (FHs) and summarised using functional principal component analysis. In our main analysis, association with case-control status is assessed using a Swedish population-based case-control study (1,170 cases and 1283 controls), for which digitised mammograms were available. We also carried out a small validation study based on digital images. RESULTS: For our main analysis, we obtained a global p value of 2×10(-7) indicating a significant association between the spatial relations of the four segmented regions and breast cancer status after adjustment for percentage density and other important breast cancer risk factors. Our (spatial relations) score had a per standard deviation odds ratio 1.29, after accounting for overfitting (percentage density had a per standard deviation odds ratio of 1.34). The spatial relations between the fatty and semi-fatty tissue and the spatial relations between the fatty and dense tissue were the most significant. The spatial relations between the fatty and semi-fatty tissue were associated with parity and age at first birth (p=6×10(-4)). Using digital images, we were able to verify that the same characteristics of tissue organisation can be identified and we validated the association for the spatial relations between the fatty and semi-fatty tissue. CONCLUSIONS: Our findings are consistent with the notion that fibroglandular and adipose tissue plays a role in breast cancer risk and, more specifically, they suggest that fatty tissue in the lower quadrants and the absence of density in the retromammary space, as shown in mediolateral oblique images, are protective against breast cancer.