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Simple Summary: In breast cancer, the leading cancer type and the main cause of cancer death in women, achieving pathological complete response after neoadjuvant chemotherapy has been shown to be associated with prolonged overall survival. Hence, the correct assessment and the potential prediction of therapy response have recently become the focus of research. In this study, we predicted pathological complete response prior to neoadjuvant system therapy using 18F-FDG PET/MRI radiomics analysis of the breast. Hence, simultaneous 18F-FDG PET/MRI may enable a more individualized and targeted approach to treatment as well as pretherapeutic patient stratification. Background: The aim of this study was to assess whether multiparametric 18F-FDG PET/MRI-based radiomics analysis is able to predict pathological complete response in breast cancer patients and hence potentially enhance pretherapeutic patient stratification. Methods: A total of 73 female patients (mean age 49 years; range 27–77 years) with newly diagnosed, therapy-naive breast cancer underwent simultaneous 18F-FDG PET/MRI and were included in this retrospective study. All PET/MRI datasets were imported to dedicated software (ITK-SNAP v. 3.6.0) for lesion annotation using a semi-automated method. Pretreatment biopsy specimens were used to determine tumor histology, tumor and nuclear grades, and immunohistochemical status. Histopathological results from surgical tumor specimens were used as the reference standard to distinguish between complete pathological response (pCR) and noncomplete pathological response. An elastic net was employed to select the most important radiomic features prior to model development. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for each model. Results: The best results in terms of AUCs and NPV for predicting complete pathological response in the entire cohort were obtained by the combination of all MR sequences and PET (0.8 and 79.5%, respectively), and no significant differences from the other models were observed. In further subgroup analyses, combining all MR and PET data, the best AUC (0.94) for predicting complete pathologic response was obtained in the HR+/HER2− group. No difference between results with/without the inclusion of PET characteristics was observed in the TN/HER2+ group, each leading to an AUC of 0.92 for all MR and all MR + PET datasets. Conclusion: 18F-FDG PET/MRI enables comprehensive high-quality radiomics analysis for the prediction of pCR in breast cancer patients, especially in those with HR+/HER2− receptor status. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to compare the diagnostic value of a one-step to a two-step staging algorithm utilizing 18F-FDG PET/MRI in breast cancer patients.Methods: A total of 38 patients (37 females and one male, mean age 57 ± 10 years; range 31-78 years) with newly diagnosed, histopathologically proven breast cancer were prospectively enrolled in this trial. All PET/MRI examinations were assessed for local tumor burden and metastatic spread in two separate reading sessions: (1) One-step algorithm comprising supine whole-body 18F-FDG PET/MRI, and (2) Two-step algorithm comprising a dedicated prone 18F-FDG breast PET/MRI and supine whole-body 18F-FDG PET/MRI.Results: On a patient based analysis the two-step algorithm correctly identified 37 out of 38 patients with breast carcinoma (97%), while five patients were missed by the one-step 18F-FDG PET/MRI algorithm (33/38; 87% correct identification). On a lesion-based analysis 56 breast cancer lesions were detected in the two-step algorithm and 44 breast cancer lesions could be correctly identified in the one-step 18F-FDG PET/MRI (79%), resulting in statistically significant differences between the two algorithms (p = 0.0015). For axillary lymph node evaluation sensitivity, specificity and accuracy was 93%, 95 and 94%, respectively. Furthermore, distant metastases could be detected in seven patients in both algorithms.Conclusion: The results demonstrate the necessity and superiority of a two-step 18F-FDG PET/MRI algorithm, comprising dedicated prone breast imaging and supine whole-body imaging, when compared to the one-step algorithm for local and whole-body staging in breast cancer patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify new disease-related circulating miRNAs with high diagnostic accuracy for breast cancer (BC) and to correlate their deregulation with the morpho-functional characteristics of the tumour, as assessed in vivo by positron emission tomography/magnetic resonance (PET/MR) imaging. A total of 77 untreated female BC patients underwent same-day PET/MR and blood collection, and 78 healthy donors were recruited as negative controls. The expression profile of 84 human miRNAs was screened by using miRNA PCR arrays and validated by real-time PCR. The validated miRNAs were correlated with the quantitative imaging parameters extracted from the primary BC samples. Circulating miR-125b-5p and miR-143-3p were upregulated in BC plasma and able to discriminate BC patients from healthy subjects (miR-125-5p area under the receiver operating characteristic ROC curve (AUC) = 0.85 and miR-143-3p AUC = 0.80). Circulating CA15-3, a soluble form of the transmembrane glycoprotein Mucin 1 (MUC-1) that is upregulated in epithelial cancer cells of different origins, was combined with miR-125b-5p and improved the diagnostic accuracy from 70% (CA15-3 alone) to 89% (CA15-3 plus miR-125b-5p). MiR-143-3p showed a strong and significant correlation with the stage of the disease, apparent diffusion coefficient (ADCmean), reverse efflux volume transfer constant (Kepmean) and maximum standardized uptake value (SUVmax), and it might represent a biomarker of tumour aggressiveness. Similarly, miR-125b-5p was correlated with stage and grade 2 but inversely correlated with the forward volume transfer constant (Ktransmean) and proliferation index (Ki67), suggesting a potential role as a biomarker of a relatively more favourable prognosis. In situ hybridization (ISH) experiments revealed that miR-143-3p was expressed in endothelial tumour cells, miR-125-5p in cancer-associated fibroblasts, and neither in epithelial tumour cells. Our results suggested that miR-125-5p and miR-143-3p are potential biomarkers for the risk stratification of BC, and Kaplan-Maier plots confirmed this hypothesis. In addition, the combined use of miR-125-b-5p and CA15-3 enhanced the diagnostic accuracy up to 89%. This is the first study that correlates circulating miRNAs with in vivo quantified tumour biology through PET/MR biomarkers. This integration elucidates the link between the plasmatic increase in these two potential circulating biomarkers and the biology of untreated BC. In conclusion, while miR-143-3b and miR-125b-5p provide valuable information for prognosis, a combination of miR-125b-5p with the tumour marker CA15-3 improves sensitivity for BC detection, which warrants consideration by further validation studies. [ABSTRACT FROM AUTHOR]