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PURPOSE. Ultrasound tomography (UST) using SoftVue (Delphinus Medical Technologies, Inc.) has the unique ability to provide quantitative whole breast tissue stiffness, including localized measurements on masses. Conversely, handheld ultrasound (HHUS) only provides localized diagnostic information of tissue stiffness, or elasticity. Screening requires global assessment of tissue properties for which HHUS is not suitable, while automated breast ultrasound does not measure stiffness. This study is the first to evaluate imaging of tissue stiffness by SoftVue for common breast masses. METHOD AND MATERIALS. Patients with findings on mammography during the time period of January 2017 to November 2018, were scanned with SoftVue. Patients were selected on the basis of having dense breasts and having either benign or malignant breast masses. All women received standard breast imaging evaluation prior to biopsy. Pathology and/or radiology reports were used as the ground truth for verifying lesion type, which included 195 masses RESULTS. SoftVue demonstrated the ability to measure tissue stiffness throughout the breast and to characterize mass stiffness in all 195 patients. Table 1 lists the average stiffness index for each type of mass. Cysts, fibroadenomas and cancers were found to have mean stiffness indices of (0.10; 95% CI: 0.05 to 0.30), (0.35; 0.25 to 0.77) and (0.60; 0.41 to 1.00) respectively (p DISCUSSION. Masses were characterized using mean stiffness and mean homogeneity of stiffness. Both measures were able to separate the populations of the three types of masses, but the homogeneity texture parameter showed less overlap between benign and malignant masses. Further radiomics analyses of texture features will assure inclusion in a future CAD tool for improved diagnostic performance. During dense breast screening by SoftVue, whole breast tissue stiffness improves cancer conspicuity throughout a breast volume for initial detection during screening, while mass characterization on the basis of stiffness may improve screening specificity, which is not possible with current ultrasound. CONCLUSION. Measuring tissue stiffness throughout the whole breast is not currently available clinically. The study demonstrates that stiffness characterization of lesions derived from whole breast stiffness imaging with UST SoftVue is feasible for future screening of women with dense breasts. Using SoftVue stiffness has the potential to reduce call backs and biopsies, in combination with other parameters, to improve specificity. Citation Format: Neb Duric, Peter J Littrup, Cuiping Li, Rachel Brem. Whole breast tissue stiffness and mass characterization by ultrasound tomography [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-02-08.