Abstract Purpose: Early detection of breast cancer through mammography screening reduces breast cancer mortality. To improve outcomes from screening, more than half of invasive cancers and a third of high grade cancers should be small at detection (<15mm), and more than 70% of all cancers should be node negative at diagnosis. Although breast density is associated with reduced mammographic sensitivity, it is unclear whether certain tumor characteristics associated with poorer prognosis are more prevalent in women with denser breasts. The study investigated associations between visually- or volumetrically-assessed breast density and tumor characteristics related to poor prognosis. Methods: Our IRB-approved study included 755 DCIS, invasive ductal or invasive lobular breast cancers diagnosed in women (aged over 40) between January 2009 and December 2012. Information on the patients' tumor characteristics including stage, size, receptor, grade and lymph node status was collected retrospectively. Women were excluded if they had a previous history of breast cancer or breast surgery, or if they were missing tumour size data or raw digital mammograms taken within 24 months of the cancer diagnosis. For women with multiple cancers, only the first diagnosed cancer was included. Breast density was assessed using visual BI-RADS density categories and Volpara Density Grades (VDG; an automated equivalent to 4th Edition BI-RADS, assigned using preset cut-offs of volumetric breast density: 4.5, 7.5, 15.5 and >15.5%). VDG was calculated from both breasts if the prior negative mammogram was available, and the contralateral breast for positive mammograms. Results: Overall, 55% of invasive tumors and 33% of grade 3 tumors were smaller than 15 mm and 83% were node negative. Mean tumor size increased significantly with increasing VDG (VDG 1 = 12.8, 2 = 14.7, 3 = 16.1, 4 = 20.4 mm, p<0.001) and increasing BI-RADS (1 = 12.2, 2 = 13.9, 3 = 16.8, 4 = 18.2 mm, p=0.01). The proportion of node positive tumors also increased significantly with increasing VDG (5.1%, 12.8%, 19.3%, 26.1%, p<0.001) and BI-RADS (0%, 10.6%, 19.5%, 26%, p=0.01). There was a significant increase in grade 3 tumors (11%, 16.1%, 21.7%, 21.7%, p =0.02) and HER-2 positive tumors (5.6%, 10.5%, 13.3%, 14.3%, p=0.02) with increasing VDG that was not seen with visual BI-RADS assessment (p=0.4). Increasing VDG was also significantly associated with increased proportions of larger (i.e. >15mm) node positive cancers (1.7%, 6.3%, 10.5%, 16%, p=0.004) that were not seen with BI-RADS (p=0.2). Conclusion: We found that tumour size and node status differed significantly with breast density as measured by VDG and visual BI-RADS. However, grade 3, HER-2 positive and large/node-positive cancers were all significantly associated with increasing VDG, but not BI-RADS density grade. Further research is needed to investigate whether automated volumetric breast density can be used to predict which women are more likely to be diagnosed with tumours that have poorer prognostic features. Citation Format: Johnston L, Chan A, Arieno A, Morgan R, Highnam R, Destounis S. Volumetric breast density better predicts tumour characteristics associated with poor prognosis compared to visual BI-RADS. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-10-12.