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Background: This study prospectively investigates the agreement between radial (r-US) and meander-like (m-US) breast ultrasound with regard to lesion location, lesion size, morphological characteristics and final BI-RADS classification of individual breast lesions., Methods: Each patient of a consecutive, unselected, mixed collective received a dual ultrasound examination., Results: The agreement between r-US and m-US for lesion location ranged from good (lesion to mammilla distance ICC 0.64; lesion to skin distance ICC 0.72) to substantial (clock-face localization κ 0.70). For lesion size the agreement was good (diameter ICC 0.72; volume ICC 0.69), for lesion margin and architectural distortion it was substantial (κ 0.68 and 0.70, respectively). Most importantly, there was a substantial agreement (κ 0.76) in the final BI-RADS classification between r-US and m-US., Conclusions: Our recent comparison of radial and meander-like breast US revealed that the diagnostic accuracy of the two scanning methods was comparable. In this study, we observe a high degree of agreement between m-US and r-US for the lesion description (location, size, morphology) and final BI-RADS classification. These findings corroborate that r-US is a suitable alternative to m-US in daily clinical practice. Trial registration NCT02358837. Registered January 2015, retrospectively registered https://clinicaltrials.gov/ct2/results?cond=&term=NCT02358837&cntry=&state=&city=&dist =.

Purpose: To prospectively compare the diagnostic accuracy of radial breast ultrasound (r-US) to that of conventional meander-like breast ultrasound (m-US), patients of a consecutive, unselected, mixed collective were examined by both scanning methods., Methods: Out of 1948 dual examinations, 150 revealed suspicious lesions resulting in 168 biopsies taken from 148 patients. Histology confirmed breast cancers in 36 cases. Sensitivity, specificity, accuracy, PPV, and NPV were calculated for r-US and m-US. The examination times were recorded., Results: For m-US and r-US, sensitivity (both 88.9%), specificity (86.4% versus 89.4%), accuracy (86.9% versus 89.3%), PPV (64.0% versus 69.6%), NPV (both 98.3%), false-negative rate (both 5.6%), and rate of cancer missed by one method (both 5.6%) were similar. The mean examination time for r-US (14.8 min) was significantly (p < 0.01) shorter than for m-US (22.6 min)., Conclusion: Because the diagnostic accuracy of r-US and m-US are comparable, r-US can be considered an alternative to m-US in routine breast US with the added benefit of a significantly shorter examination time.

Real-time elastography (RTE) is a noninvasive imaging modality where tumor-associated changes in tissue architecture are recognized as increased stiffness of the lesion compared to surrounding normal tissue. In contrast to this macroscopic appraisal, quantifying stiffness properties at the subcellular level by atomic force microscopy (AFM) reveals aggressive cancer cells to be soft. We compared RTE and AFM profiling of the same breast lesion to explore the diagnostic potential of tissue elasticity at different length scales. Patients were recruited from women who were scheduled for a biopsy in the outpatient breast clinic of the University Hospital Basel, Switzerland. RTE was performed as part of a standard breast work-up. Individual elastograms were characterized based on the Tsukuba elasticity score. Additionally, lesion elasticity was semiquantitatively assessed by the strain ratio. Core biopsies were obtained for histologic diagnosis and nanomechanical profiling by AFM under near-physiological conditions. Bulk stiffness evaluation by RTE does not always allow for a clear distinction between benign and malignant lesions and may result in the false assessment of breast lesions. AFM on the other hand enables quantitative stiffness measurements at higher spatial, i.e., subcellular, and force resolution. Consequently, lesions that were false positive or false negative by RTE were correctly identified by their nanomechanical AFM profiles as confirmed by histological diagnosis. Nanomechanical measurements can be used as unique markers of benign and cancerous breast lesions by providing relevant information at the molecular level. This is of particular significance considering the heterogeneity of tumors and may improve diagnostic accuracy compared to RTE.

Our aim was to prospectively evaluate inter- and intra-observer agreement between Breast Imaging Reporting and Data System (BI-RADS) classifications and Tsukuba elasticity scores (TSs) of breast lesions. The study included 164 breast lesions (63 malignant, 101 benign). The BI-RADS classification and TS of each breast lesion was assessed by the examiner and twice by three reviewers at an interval of 2 months. Weighted κ values for inter-observer agreement ranged from moderate to substantial for BI-RADS classification (κ = 0.585-0.738) and was substantial for TS (κ = 0.608-0.779). Intra-observer agreement was almost perfect for ultrasound (US) BI-RADS (κ = 0.847-0.872) and TS (κ = 0.879-0.914). Overall, individual reviewers are highly self-consistent (almost perfect intra-observer agreement) with respect to BI-RADS classification and TS, whereas inter-observer agreement was moderate to substantial. Comprehensive training is essential for achieving high agreement and minimizing the impact of subjectivity. Our results indicate that breast US and real-time elastography can achieve high diagnostic performance., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Cancer initiation and progression follow complex molecular and structural changes in the extracellular matrix and cellular architecture of living tissue. However, it remains poorly understood how the transformation from health to malignancy alters the mechanical properties of cells within the tumour microenvironment. Here, we show using an indentation-type atomic force microscope (IT-AFM) that unadulterated human breast biopsies display distinct stiffness profiles. Correlative stiffness maps obtained on normal and benign tissues show uniform stiffness profiles that are characterized by a single distinct peak. In contrast, malignant tissues have a broad distribution resulting from tissue heterogeneity, with a prominent low-stiffness peak representative of cancer cells. Similar findings are seen in specific stages of breast cancer in MMTV-PyMT transgenic mice. Further evidence obtained from the lungs of mice with late-stage tumours shows that migration and metastatic spreading is correlated to the low stiffness of hypoxia-associated cancer cells. Overall, nanomechanical profiling by IT-AFM provides quantitative indicators in the clinical diagnostics of breast cancer with translational significance.

Cells constantly encounter physical forces and respond to neighbors and circulating factors by triggering intracellular signaling cascades that in turn affect their behavior. The mechanisms by which cells transduce mechanical signals to downstream biochemical changes are not well understood. In their work, Salaita and coworkers show that the spatial organization of cell surface receptors is crucial for mechanotransduction. Consequently, force modulation that disrupts the mechanochemical coupling may represent a critical step in cancerogenesis.