Objective: Full-field digital mammography (FFDM) has limited sensitivity for cancer in younger women with denser breasts. Digital breast tomosynthesis (DBT) can reduce the risk of cancer being obscured by overlying tissue. The primary study aim was to compare the sensitivity of FFDM, DBT and FFDM-plus-DBT in women under 60 years old with clinical suspicion of breast cancer. Methods: This multicentre study recruited 446 patients from UK breast clinics. Participants underwent both standard FFDM and DBT. A blinded retrospective multireader study involving 12 readers and 300 mammograms (152 malignant and 148 benign cases) was conducted. Results: Sensitivity for cancer was 86.6% with FFDM [95% CI (85.2–88.0%)], 89.1% with DBT [95% CI (88.2–90%)], and 91.7% with FFDM+DBT [95% CI (90.7–92.6%)]. In the densest breasts, the maximum sensitivity increment with FFDM +DBT over FFDM alone was 10.3%, varying by density measurement method. Overall specificity was 81.4% with FFDM [95% CI (80.5–82.3%)], 84.6% with DBT [95% CI (83.9–85.3%)], and 79.6% with FFDM +DBT [95% CI (79.0–80.2%)]. No differences were detected in accuracy of tumour measurement in unifocal cases. Conclusions: Where available, DBT merits first-line use in the under 60 age group in symptomatic breast clinics, particularly in women known to have very dense breasts. Advances in knowledge: This study is one of very few to address the accuracy of DBT in symptomatic rather than screening patients. It quantifies the diagnostic gains of DBT in direct comparison with standard digital mammography, supporting informed decisions on appropriate use of DBT in this population.

Background Elastin degradation has been implicated in the pathophysiology of vulnerable atherosclerotic plaque. Desmosine is the cross-link component in the elastin molecule and is exclusively released from mature elastin breakdown, thus has the potential to be a physiologically relevant biomarker of atherosclerosis. Objectives The aim of the present study was: 1. To investigate whether patients with known cardiovascular disease (CVD) have higher elastin degradation as indicated by plasma desmosine (pDES); 2. to determine the relationship between pDES and total atherosclerotic burden. Methods We measured pDES by a validated stable isotope dilution LC-MS/MS method1 in a total of 146 subjects from the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study2. (62% male, mean age 64±8 (SD) years). This included 62 patients with prior clinical diagnosis of CVD (including coronary artery disease (CAD), cerebrovascular disease and/or lower extremity arterial disease (LEAD)), and 84 patients without a clinical diagnosis of CVD. Total atherosclerotic burden was measured by whole body magnetic resonance angiography (WB-MRA). The WB-MRA data was divided into 31 anatomical arterial segments with each segment scored according to degree of luminal narrowing: 0 = no stenosis, 1 = <50% stenosis, 2 = 51–70% stenosis, 3 = 71–99% stenosis, 4 = vessel occlusion. The segment scores were summed and from this, a standardized atheroma score (SAS) was calculated by summing each individual segment's stenosis score, and divided by the number of diagnostic segments before dividing by 4 which is the maximum potential score. Relationship between SAS and pDES levels was investigated using multiple linear regression models Results pDES levels were significantly greater in patients with established clinical CVD compared to patients with no CVD (CVD patients, 0.56 (0.45–0.67) ng/mL; patients with no CVD, 0.47 (0.41–0.54)ng/mL; p=0.001). Median SAS for the study population was 4 (2–10). Overall pDES levels showed a strong correlation with SAS (r=0.44, p≤0.001). Univariable analysis suggested a significant association between pDES and whole-body atheroma score as measured by SAS. (β 29.31, p<0.001). This association persisted in the multivariable regression model adjusting for traditional cardiovascular risk factors including age, gender, BMI, systolic blood pressure, diabetes, smoking status and LDL. (adjusted β 18.75, p=0.004) Conclusion pDES levels are elevated in patients with clinical CVD when compared to those with no clinical history of CVD. pDES is also strongly associated with global atheroma burden. Overall, these findings support the role of pDES as a potential biomarker for atherosclerosis. Funding Acknowledgement Type of funding sources: None.