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PURPOSE. Studies have shown that a decrease in mammographic density (MD) or lowering of background parenchymal enhancement (BPE) on MRI after initiation of tamoxifen therapy predicts a favorable response in the preventive or adjuvant settings. However, performing serial mammograms poses radiation concerns, while serial MRIs carry high cost as well as risk of multiple Gadolinium doses. Previous studies have shown that tissue sound speed, derived from whole breast ultrasound tomography measurements, is a surrogate biomarker of MD. Ultrasound is ideal for performing serial measurements because it is fast and poses almost no risks. The purpose of this study was to evaluate repeated measures of the sound speed biomarker at 3, 6 and 12-months following tamoxifen initiation. METHOD AND MATERIALS. We performed a case-control comparison involving 74 participants referred by a health professional to undergo tamoxifen therapy (cases) and 150 matched participants with no history of breast cancer (controls). The cases were scanned with ultrasound tomography at baseline (i.e. before start of tamoxifen therapy), and then at 3, 6 and 12 months after tamoxifen initiation. Controls were scanned at baseline and 12 months. In the case group, sound speed was measured pre-treatment in the contralateral breast to avoid potential influences of tumor-related changes on density. In the control group, a single randomized breast was scanned. A pairwise t-test was used to assess differences in sound speed over time and between cases and controls. RESULTS. There was a steady decline in sound speed over the 12-month period for women undergoing tamoxifen therapy (mean(SD): -3.0(8.2) m/s; P=0.001). Furthermore, significant sound speed reductions were observed as early as 4-6 months after tamoxifen initiation (mean(SD): -2.1(6.8) m/s; P=0.008). In contrast, the controls demonstrated no significant change in sound speed over a 12-month period, and the difference between case-control groups was statistically significant (P=0.0009). DISCUSSION. Breast sound speed decreases rapidly after tamoxifen initiation while it remains steady for the control group. These results suggest that sound speed may be a biomarker of response to tamoxifen. Further studies are needed to assess whether this observation can predict clinical response. CONCLUSION. Ultrasound tomography may have utility in monitoring breast sound speed change as a potential biomarker of clinical tamoxifen response. Citation Format: Neb Duric, Mark Sak, Mark Sherman, Ruth Pfeiffer, Sharon Fan, Michael Simon, David Gorski, Teri Albrecht, Haythem Ali, Peter Littrup, Rachel Brem, Gretchen Gierach. Tissue sound speed: A novel imaging biomarker for measuring tamoxifen response [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 P2-11-11.

PURPOSE. Increased mammographic percent density (MPD) is a strong independent risk factor for developing breast cancer. Previous studies have shown that tissue sound speed, derived from ultrasound tomography, is a surrogate biomarker of MPD. We examined associations of sound speed and MPD with breast cancer risk in a case-control study. METHOD AND MATERIALS. We evaluated breast cancer risk associated with sound speed and MPD in a case-control study involving 59 participants with recent breast cancer diagnoses (cases, aged 30-70 years) and 150 participants with no history of breast cancer (controls), who were matched to cases on age, race, and menopausal status. The cases and controls were imaged with both ultrasound tomography (UST) and mammography. In cases, breast density was measured pre-treatment in the contralateral breast to avoid potential influences of tumor-related changes on MPD or sound speed. In controls, a randomly selected breast was imaged. The ultrasound tomography images were used to estimate the volume averaged sound speed of the breast, and the Cumulus software package was applied to mammograms to determine MPD. Odds Ratios (ORs) and 95% Confidence Intervals (CIs), adjusted for matching factors, were calculated for the relation of quartiles of MPD and sound speed with breast cancer risk. OR differences were tested using a bootstrap approach. RESULTS. MPD was associated with elevated breast cancer risk compared to controls, consistent with previous studies, although the trend did not reach statistical significance (OR per quartile=1.28, 95%CI: 0.95, 1.73; ptrend=0.10). In contrast, elevated sound speed was significantly associated with increased breast cancer risk in a dose-response fashion (OR per quartile=1.79, 95%CI: 1.30, 2.48; ptrend=0.0004). The OR-trend for sound speed was statistically significantly different from that observed for MPD (p=0.01). DISCUSSION. Our case-control study showed that increasing quartiles of whole breast sound speed were consistently and more strongly associated with increasing breast cancer risk than quartiles of MPD. These results show promise for UST’s role in breast cancer risk stratification. CONCLUSION. Elevated breast density strongly increases breast cancer risk. UST has the potential to provide a more accurate, non-ionizing method for assessing breast density and its associated breast cancer risk. Citation Format: Mark Sak, Neb Duric, Ruth Pfeiffer, Mark Sherman, Peter Littrup, Michael Simon, David Gorski, Teri Albrecht, Haythem Ali, Rachel Brem, Rachel Brem, Sharon Fan, Gretchen Gierach. Tissue sound speed is more strongly associated with breast cancer risk than mammographic percent density: A comparative case-control study [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 P3-08-28.

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. Table 1Type of MassStiffness index valueStandard deviation95% CIMean HomogeneityStandard Deviation95% CICyst0.100.200.05-0.300.830.050.73 - 0.91FB0.350.240.25-0.770.770.060.65 - 0.85Ca0.610.190.41-1.000.660.090.52 - 0.79 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.

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 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 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.