Abstract PR09: Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to the status of selected tissue markers: A case-control study
Authors: Yaghjyan Lusine , Pettersson Andreas , Colditz Graham , Collins Laura , Schnitt Stuart , Beck Andrew , Rosner Bernard , Vachon Celine , Tamimi Rulla 
Published: May 2019

Abstract
Background: This analysis aimed to determine if associations of prediagnostic mammographic percent breast density, absolute dense area, and absolute non-dense area and risk of breast cancer vary according to the subsequent breast tumors biomarker status. Methods: We included 1,154 postmenopausal women diagnosed with breast cancer between June 1, 1989, and June 30, 2004, and 2,078 matched controls from the Nurses' Health Study I and II. Percent breast density, absolute dense and non-dense areas were estimated from digitized film mammograms using computer assisted thresholding techniques. Density measures were modeled as quartiles. Information on estrogen receptor (ESR1 [ER]), progesterone receptor (PGR [PR]), and human epidermal growth factor receptor 2 (ERBB2 [HER2]) status was obtained from pathology reports and medical records, and if missing, from immunostains performed on paraffin sections of tumor tissue microarrays (TMAs). Other biomarkers assessed on TMAs were androgen receptor (AR), cytokines 5/6 (KRT5/KRT6 [CK5/6]), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGFA [VEGF]), and cyclooxygenase 2 (PTGS2 [COX2]). Information on breast cancer risk factors was obtained prospectively from biennial questionnaires before the date of cancer diagnosis for cases and matched controls. Polychotomous logistic regression was used to assess associations of the three breast density measures with tumor subtypes based on the status of selected tissue markers. Results: Breast cancer risk was positively associated with percent density and absolute dense area and inversely associated with absolute non-dense area (p for trend&lt;0.0001 for all). The associations of percent density with breast cancer risk did not statistically significantly differ by the status of any of the markers. However, we found stronger positive associations for absolute dense area and KRT5/KRT6- and EGFR- tumors as compared to respective marker-positive tumors (4th vs. 1st quartile: OR=2.99 for KRT5/KRT6- vs. OR=0.92 for KRT5/KRT6+ tumors, p-heterogeneity &lt;0.001; OR=3.06 for EGFR- vs. OR=1.08 for EGFR+ tumors, p-heterogeneity=0.001). Stronger inverse associations of absolute non-dense area with breast cancer risk were found for ESR1- as compared to ESR1+ tumors, and for AR+, KRT5/KRT6+, and EGFR+ tumors as compared to respective marker-negative tumors (4th vs. 1st quartile: OR=0.21 for ESR1- vs. OR=0.59 for ESR1+ tumors, p-heterogeneity &lt;0.0001; OR=0.22 for AR+ vs. OR=0.42 for AR- tumors, p-heterogeneity=0.04; OR=0.21 for KRT5/KRT6+ vs. OR=1.14 for KRT5/KRT6- tumors, p-heterogeneity&lt;0.01; OR=0.37 for EGFR+ vs. OR=1.11 for EGFR- tumors, p-heterogeneity&lt;0.01). There were no differences in associations of the density measures with breast cancer by status of other markers evaluated. Conclusions: The findings suggest that some mammographic density measures are differentially associated with the risk of subsequent breast tumor subtypes.
Citation Format: Lusine Yaghjyan, Andreas Pettersson, Graham Colditz, Laura Collins, Stuart Schnitt, Andrew Beck, Bernard Rosner, Celine Vachon, Rulla Tamimi. Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to the status of selected tissue markers: A case-control study. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PR09.