Abstract Introduction: Breast density is a strong risk factor for breast cancer. Several studies found Black women to have lower breast density than white women on average, which may be partly due to racial differences in BMI, which is inversely associated with density. Our study utilizes fully-automated, validated quantitative measurements of both area and volumetric breast density. We assess racial differences in these novel measures, accounting for age, BMI, and other established breast cancer risk factors. Methods: From women who underwent mammography screening at our institution in 2010-11, we analyzed all available raw digital mammograms for women who had BMI recorded in electronic medical records at the time of screening. A previously-validated, publically-available, fully-automated software algorithm developed in our institution was used to generate per-woman estimates of absolute and percent area density. Volumetric estimates of absolute and percent dense tissue were obtained using FDA-cleared software (Quantra™, Hologic, Inc). Women identified as White or Black/African American with no prior history of breast cancer were included (N = 2845). Patient characteristics and mean density measures were compared by race using Chi-square tests and t-tests. Density measures were log-transformed and z-score standardized. Linear regression was performed to assess racial differences in mean density measures, adjusted for age, BMI, and breast cancer risk factors (prior biopsy, age at menarche, menopause status, family history, age at first birth, HRT use). We also tested the interaction of race and BMI on density. Results: The mean age of patients was 57, and was similar for white and black women (p = .159). Black women had higher mean BMI than white women (32.0 kg/m2 vs. 26.0 kg/m2, p<.001). Black women had higher absolute area (40.1 vs. 33.1 cm2, p<.001) and volume (187.2 vs. 181.6 cm3, p<.001) density than white women, but lower area (19.6% vs. 23.5%, p<.001) and volume percent density (11.6% vs. 13.4%, p<.001). After adjusting for age, BMI, and breast cancer risk factors, black women had higher breast density across all measures (absolute area density β = 0.211 p<0.001, area percent density β = 0.099 p = .021, absolute volume density β = 0.242 p<.001, volume percent density β = 0.221 p<.001). The interaction between race and BMI was significant for area percent (p = .001) and volume percent density (p<.001), and near significant for volume density (p = .085). For all three measures, BMI was more strongly associated with density among white women than black women. Conclusions: Black women had significantly higher breast density than whites using quantitative measurements which was not explained by BMI or recognized breast cancer risk factors. Furthermore, the association of BMI with density was weaker in black women than white women. Such racial differences in breast density and its association with BMI may have implications for disease risk and prevention strategies. Citation Format: Anne Marie McCarthy, Brad Keller, Marie Synnestvedt, Emily Conant, Katrina Armstrong, Despina Kontos. Racial differences in quantitative measures of area and volumetric breast density. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2770. doi:10.1158/1538-7445.AM2015-2770