Breast radiation dose with contrast-enhanced mammography-guided biopsy: a retrospective comparison with stereotactic and tomosynthesis guidance.

OBJECTIVES: This retrospective study aimed to compare the average glandular dose (AGD) per acquisition in breast biopsies guided by contrast-enhanced mammography (CEM), conventional stereotactic breast biopsy (SBB), and digital breast tomosynthesis (DBT). The study also investigated the influence of compressed breast thickness (CBT) and density on AGD. Furthermore, the study aimed to estimate the AGD per procedure for each guidance modality. METHODS: The study included 163 female patients (mean age 57 ± 10 years) who underwent mammography-guided biopsies using SBB (9%), DBT (65%), or CEM (26%) guidance. AGD and CBT data were extracted from DICOM headers, and breast density was visually assessed. Statistical analyses included two-sample t-tests and descriptive statistics. RESULTS: Mean AGD per acquisition varied slightly among CEM (1.48 ± 0.22 mGy), SBB (1.49 ± 0.40 mGy), and DBT (1.55 ± 0.47 mGy), with CEM presenting higher AGD at lower CBTs and less dose escalation at higher CBTs. For CBT > 55 mm, CEM showed reduced AGD compared to SBB and DBT (p < 0.001). Breast density had minimal impact on AGD, except for category A. The estimated AGD per procedure was approximately 11.84 mGy for CEM, 11.92 mGy for SBB, and 6.2 mGy for DBT. CONCLUSION: The study found mean AGD per acquisition to be similar for CEM and SBB, with DBT slightly higher. CEM demonstrated higher AGD at lower CBT but lower AGD at higher CBT, indicating reduced dose escalation with increasing thickness. While breast density had minimal overall impact, variations were noted in category A. DBT was more dose-efficient per procedure due to fewer acquisitions required. CLINICAL RELEVANCE STATEMENT: CEM guidance provides effective lesion visualization within safe radiation limits, improving the precision of percutaneous image-guided breast interventions and supporting its potential consideration in a wider range of breast diagnostic procedures. KEY POINTS: Limited data exist on the AGD using CEM guidance for breast biopsies. CEM and SBB exhibit similar AGD per acquisition; DBT demonstrated the lowest AGD per procedure. Radiation from CEM guidance fits within safe limits for percutaneous image-guided breast interventions.

Accuracy of sentinel node mapping in patients with biopsy-proven metastatic axillary lymph nodes and upfront surgery: preliminary results of the Multimodal Targeted Axillary Surgery (MUTAS) trial.

Background: Some studies suggested that the patients included in the Z0011 trial may represent patients with ultrasound-negative axillary nodes and axillary invasion diagnosed by sentinel node (SN) biopsy. Nevertheless, the National Comprehensive Cancer Network (NCCN) guidelines recommend SN mapping if 1 or 2 suspicious lymph nodes are identified on axillary ultrasound (AU). The aim of this preliminary phase of the Multimodal Targeted Axillary Surgery (MUTAS) trial was to establish the accuracy of SN mapping in patients with axillary involvement undergoing upfront surgery. Methods: Between September 2019 and March 2022, we recruited patients with biopsy-proven metastatic axillary nodes and upfront surgery from a single center. We performed SN mapping in these patients before the surgical intervention, which included axillary lymph node dissection. The biopsy-proven metastatic node, SNs and the remaining axillary nodes were excised separately. SN status was considered representative of the status of the remaining axillary nodes. We calculated the sensitivity, specificity, negative predictive value and positive predictive value of the SN, overall and in patients with palpable nodes, in those with non-palpable nodes and an AU leading to diagnosis of axillary involvement, in those with 1 or 2 suspicious nodes on AU, and in patients with a single suspicious node on AU. We evaluated clinical, imaging and pathology features as predictors of the status of the remaining axillary nodes, false-negatives, and false-positives. Results: We included 25 patients in this phase. The false-negative rate of SN mapping was 28% overall, 21.42% for patients with palpable nodes, 36.36% for patients with non-palpable nodes and an AU diagnosis of axillary involvement, 28.75% for those with 1 or 2 suspicious nodes on AU, and 15.38% in patients with a single suspicious node on AU. The negative predictive value was highest in patients with a single suspicious node on AU (75%). The only significant predictive factor was that FN showed a higher Ki67 index score. Conclusions: In this study, SN mapping was not reliable in patients with biopsy-proven metastatic axillary nodes and upfront surgery for any of the subgroups studied. Further research should elucidate the best staging pathways in these patients to avoid premature de-escalation.

Comparison of technical parameters and women's experience between self-compression and standard compression modes in mammography screening: a single-blind randomized clinical trial.

OBJECTIVES: We compared the compression force, breast thickness, and glandular dose, as well as the severity of discomfort and women's experience between the patient-assisted compression (PAC) and standard compression (SC) modes. MATERIALS AND METHODS: We conducted a prospective randomized controlled study at Hospital del Mar in Barcelona, Spain. We included 448 asymptomatic women aged 50 to 69 years old, attending their screening round from December 2017 to December 2019. Mammograms included the two bilateral views. In each woman, one breast was studied with SC and the other with PAC. The mode used in each breast was selected following a randomized list. Compression force, breast thickness, and average glandular dose were obtained for each of the 1792 images. We also recorded the degree of discomfort and women's experience, after mammogram acquisitions, using a predefined survey. RESULTS: Higher compression forces were obtained with PAC than with SC (99.27 N vs 83.25 N, p < 0.001). Breast thickness mode (56.11 mm vs 57.52 mm, p = 0.015) and glandular dose (1.34 mGy vs 1.37 mGy, p = 0.018) were lower in PAC. The discomfort score was slightly higher with PAC (mean 3.94 vs 3.69, p = 0.042), but in the satisfaction survey, more women reported that PAC caused less discomfort. Additionally, 63.2% of women (289/448) preferred PAC. CONCLUSION: PAC achieved higher compression forces without impairing the other technical imaging parameters and enhanced women's experience of screening mammography. We believe there were no clinically significant differences in the severity of discomfort between the two modes. KEY POINTS: • Self-compression allows higher compression forces than the standard compression mode. • Self-compression does not affect technical imaging parameters. • Self-compression improved women's experience of screening mammography when standard compression was used on one breast and self-compression on the other.

Does the patient-assisted compression mode affect the mammography quality? A within-woman randomized controlled trial.

OBJECTIVES: Evaluate the image quality of a mammography screening device using the patient-assisted compression (PAC) compared with the standard compression (SC) mode. METHODS: This prospective within-woman, randomized controlled trial was conducted between September 2017 and December 2019. Participants were asymptomatic women aged 50 to 69 years attending their second or subsequent screening mammography round. By random assignment, one breast underwent the SC and the other breast, the PAC. Image quality was evaluated as perfect, good, moderate, or inadequate (PGMI) on 10 criteria for the craniocaudal (CC) view and 8 criteria for the mediolateral oblique (MLO) view. Pearson's chi-square test, with Yates' correction if pertinent, was performed to compare image quality between compression modes. RESULTS: A total of 444 participants were included (mean [± standard deviation] age, 60 [± 4.9] years). There were no differences in the percentages of PGMI between the PAC and SC modes for the CC view (perfect, 37% [162/444] vs 37% [163/444]; good, 1% [5/444] vs 2% [9/444]; moderate, 62% [277/444] vs 61% [271/444]; inadequate, 0% vs 0.2% [1/444]; p = .88) or for the MLO view (perfect, 53% [237/444] vs 56% [247/444]; good, 22% [99/444] vs 22% [97/444]; moderate, 23% [102/444] vs 22% [98/444]; inadequate, 1% [6/444] vs 0.5% [2/444]; p = .72). No differences were found when we stratified by laterality or when analyzed by PGMI criteria. CONCLUSION: PAC does not seem to impair mammographic image quality. Future research should focus in a daily practice setting. KEY POINTS: No differences were found in the distribution of the PGMI classification, a tool for quality assessment, between patient-assisted compression and standard compression. Similar results were found on stratification of image quality by mammographic view and breast laterality for both types of compression. None of the PGMI criteria had significantly more errors in patient-assisted compression than in standard compression.

Engineering Saccharomyces cerevisiae for the Overproduction of ß-Ionone and Its Precursor ß-Carotene.

ß-ionone is a commercially attractive industrial fragrance produced naturally from the cleavage of the pigment ß-carotene in plants. While the production of this ionone is typically performed using chemical synthesis, environmentally friendly and consumer-oriented biotechnological production is gaining increasing attention. A convenient cell factory to address this demand is the yeast Saccharomyces cerevisiae. However, current ß-ionone titers and yields are insufficient for commercial bioproduction. In this work, we optimized S. cerevisiae for the accumulation of high amounts of ß-carotene and its subsequent conversion to ß-ionone. For this task, we integrated systematically the heterologous carotenogenic genes (CrtE, CrtYB and CrtI) from Xanthophyllomyces dendrorhous using markerless genome editing CRISPR/Cas9 technology; and evaluated the transcriptional unit architecture (bidirectional or tandem), integration site, and impact of gene dosage, first on ß-carotene accumulation, and later, on ß-ionone production. A single-copy insertion of the carotenogenic genes in high expression loci of the wild-type yeast CEN.Pk2 strain yielded 4 mg/gDCW of total carotenoids, regardless of the transcriptional unit architecture employed. Subsequent fine-tuning of the carotenogenic gene expression enabled reaching 16 mg/gDCW of total carotenoids, which was further increased to 32 mg/gDCW by alleviating the known pathway bottleneck catalyzed by the hydroxymethylglutaryl-CoA reductase (HMGR1). The latter yield represents the highest total carotenoid concentration reported to date in S. cerevisiae for a constitutive expression system. For ß-ionone synthesis, single and multiple copies of the carotene cleavage dioxygenase 1 (CCD1) gene from Petunia hybrida (PhCCD1) fused with a membrane destination peptide were expressed in the highest ß-carotene-producing strains, reaching up to 33 mg/L of ß-ionone in the culture medium after 72-h cultivation in shake flasks. Finally, interrogation of a contextualized genome-scale metabolic model of the producer strains pointed to PhCCD1 unspecific cleavage activity as a potentially limiting factor reducing ß-ionone production. Overall, the results of this work constitute a step toward the industrial production of this ionone and, more broadly, they demonstrate that biotechnological production of apocarotenoids is technically feasible.

Heterologous production of the epoxycarotenoid violaxanthin in Saccharomyces cerevisiae.

Microbial production of carotenoids has mainly focused towards a few products, such as ß-carotene, lycopene and astaxanthin. However, other less explored carotenoids, like violaxanthin, have also shown unique properties and promissory applications. Violaxanthin is a plant-derived epoxidated carotenoid with strong antioxidant activity and a key precursor of valuable compounds, such as fucoxanthin and ß-damascenone. In this study, we report for the first time the heterologous production of epoxycarotenoids in yeast. We engineered the yeast Saccharomyces cerevisiae following multi-level strategies for the efficient accumulation of violaxanthin. Starting from a ß-carotenogenic yeast strain, we first evaluated the performance of several ß-carotene hydroxylases (CrtZ), and zeaxanthin epoxidases (ZEP) from different species, together with their respective N-terminal truncated variants. The combined expression of CrtZ from Pantoea ananatis and truncated ZEP of Haematococcus lacustris showed the best performance and led to a yield of 1.6 mg/gDCW of violaxanthin. Further improvement of the epoxidase activity was achieved by promoting the transfer of reducing equivalents to ZEP by expressing several redox partner systems. The co-expression of the plant truncated ferredoxin-3, and truncated root ferredoxin oxidoreductase-1 resulted in a 2.2-fold increase in violaxanthin yield (3.2 mg/gDCW). Finally, increasing gene copy number of carotenogenic genes enabled reaching a final production of 7.3 mg/gDCW in shake flask cultures and batch bioreactors, which is the highest yield of microbially produced violaxanthin reported to date.