Abstract PURPOSE. Recent analyses of tumor location by breast magnetic resonance (MR) imaging have shown that breast cancers were significantly more likely to be located, at or near the fat-gland interface (FGI). However, these analyses did not include benign masses or coronal evaluations. Ultrasound tomography (UST) is a novel multi-sequence tomographic form of sonography with anatomic and physiologic information that can improve the sensitivity of breast cancer detection, particularly in women with dense breasts. The purpose of this study was to use the native coronal imaging plane of UST SoftVue (Delphinus Medical Technologies, Inc.) to map the locations of cancers, fibroadenomas and cysts, relative to the FGI, in order to facilitate the detection and characterization of breast masses in future UST screening. METHODS AND MATERIALS. Mass location in coronal UST images was determined by a MQSA certified radiologist with extensive UST imaging experience. The relationship of the lesion to the FGI was noted for a total of 427 breast masses (117 cancers, 135 fibroadenomas, 135 cysts and 40 other benign findings), confirmed by biopsy or by hand-held ultrasound for masses that fulfilled all criteria for a simple cyst. The FGI was defined as the circumferential interface between the peripheral fat and parenchyma as determined by examining sound speed (SS) images, which reliably differentiate the much lower SS of fat compared to that of dense tissue. Mass location was placed into three groups: (i) completely surrounded by dense fibroglandular tissue, (ii) completely surrounded by fat or (iii) partially surrounded by both (i.e., the FGI). Lesion locations relative to FGI were compared using the chi-squared test. RESULTS. Cancers were located at the FGI in 93.2% (109/117) of the cases and were surrounded by fat in 6.0% (7/117) or parenchyma in 0.9% (1/117) (p<0.001) of the cases, respectively (Table 1). For fibroadenomas, 63.0% (85/135) were found at the FGI while 29.9% of cysts were found at the FGI. Moreover, 68.9% of cysts and 31.1% of fibroadenomas were fully surrounded by dense tissue which was dramatically more than cancers (0.9%). DISCUSSION. Coronal imaging by UST provides reliable circumferential evaluation of the FGI, which can be augmented by axial/sagittal reconstructions as needed for additional confirmation of anterior/posterior aspects of the FGI. Our results confirm the previously reported MRI findings that cancers have a very strong tendency to be located at the FGI and extend these findings by demonstrating that benign masses have a weaker tendency in that regard. With the introduction of UST, our finding that breast cancers occur more frequently at the fat-gland interface may facilitate the conspicuity, rapid search and localization of cancers during screening of women with dense breasts. Perhaps equally important for future specificity of screening women with dense breasts, fibroglandular tissue surrounded only 0.9% of cancers and was much more commonly associated with benign masses. CONCLUSIONS. The native coronal imaging plane by SoftVue UST facilitated detection and localization of cancers, which were much more likely to be found at the FGI (p<0.001), compared to masses surrounded by fibroglandular tissue were much more likely to be benign. UST is a novel new technology that has the potential for improved breast cancer detection. This study supports its possible integration into clinical practice. Table 1Type of massAt FGIIn Dense tissueIn FatCancer109 (93%)1 (1%)7 (6%)Fibroadenoma85 (63%)42 (31%)8 (6%)Cyst39 (29%)93 (69%)3 (2%) Citation Format: Peter Littrup, Mark Sak, Neb Duric, Rachel Brem. Breast cancer development at the fat-gland interface (FGI): Importance of coronal imaging and 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 P1-02-05.