Abstract
<div>Abstract<p><b>Background:</b> Mammographic density (MD) is a strong breast cancer risk factor. We previously reported associations of percent mammographic density (PMD) with larger and node-positive tumors across all ages, and estrogen receptor (ER)–negative status among women ages <55 years. To provide insight into these associations, we examined the components of PMD [dense area (DA) and nondense area (NDA)] with breast cancer subtypes.</p><p><b>Methods:</b> Data were pooled from six studies including 4,095 breast cancers and 8,558 controls. DA and NDA were assessed from digitized film-screen mammograms and standardized across studies. Breast cancer odds by density phenotypes and age according to histopathologic characteristics and receptor status were calculated using polytomous logistic regression.</p><p><b>Results:</b> DA was associated with increased breast cancer risk [OR for quartiles: 0.65, 1.00 (Ref), 1.22, 1.55; <i>P</i><sub>trend</sub> <0.001] and NDA was associated with decreased risk [ORs for quartiles: 1.39, 1.00 (Ref), 0.88, 0.72; <i>P</i><sub>trend</sub> <0.001] across all ages and invasive tumor characteristics. There were significant trends in the magnitude of associations of both DA and NDA with breast cancer by increasing tumor size (<i>P</i><sub>trend</sub> < 0.001) but no differences by nodal status. Among women <55 years, DA was more strongly associated with increased risk of ER<sup>+</sup> versus ER<sup>−</sup> tumors (<i>P</i><sub>het</sub> = 0.02), while NDA was more strongly associated with decreased risk of ER<sup>−</sup> versus ER<sup>+</sup> tumors (<i>P</i><sub>het</sub> = 0.03).</p><p><b>Conclusions:</b> DA and NDA have differential associations with ER<sup>+</sup> versus ER<sup>−</sup> tumors that vary by age.</p><p><b>Impact:</b> DA and NDA are important to consider when developing age- and subtype-specific risk models. <i>Cancer Epidemiol Biomarkers Prev; 24(5); 798–809. ©2015 AACR</i>.</p></div>
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