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A set of protein biomarkers are largely recognized as responsible of neurodegeneration mechanisms and hence as potential targets to be detected in low abundant concentrations in body fluids for performing early diagnosis. As an example, the Tau protein experiences a transition phase from a native disorder conformation into a preaggregation state, which leads to fibrillization processes. Here we show the possibility to detect Tau in urine samples at sub-picogram level, through the concentration effect of the pyro-electrohydrodynamic (p-jet) technique. An immunofluorescence protocol is applied to concentrated p-jet spots able to reduce drastically the diffusion effects in the antibody-antigen reaction. A set of diluted samples were prepared, and the fluorescence signal was detected by a confocal scanner. We achieved an excellent linear response with a significant signal-to-noise ratio down to 0.25 pg/mL. In perspective, the technique could be integrated into a compact device to be used for monitoring the early stage associated to neurodegenerative syndromes in different scenarios such as for example in long-term human space exploration missions.

Background/objectives: HER2-positive breast cancer (HER2 + BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2 + BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting. The secondary objective was to assess the effectiveness., Methods: This was a multicenter, retrospective study across 24 Italian oncology centers, including 410 patients with HER2 + BC treated with adjuvant T-DM1 following a lack of pCR after NAT. Patient characteristics, NAT regimens, and surgical outcomes were recorded. Tolerability was assessed by documenting adverse events (AEs) according to the CTCAE (v5.0). Preliminary effectiveness was evaluated in terms of relapse-free survival (RFS) and overall survival (OS)., Results: Overall, 228 patients (55.6%) experienced at least one AE related to T-DM1, with 4.9% experiencing grade 3 or higher AEs. The most common AEs were hepatotoxicity (18.5%) and thrombocytopenia (17.6%). T-DM1 was discontinued in 10.0% of patients due to toxicity. After a median follow-up of 25 months, 31 relapse events (7.6%) and 22 deaths (5.4%) were reported. The preliminary incidence of RFS and OS events was similar between patients who completed the T-DM1 course and those who discontinued it early., Conclusions: T-DM1 demonstrated a manageable safety profile, and the adverse events were consistent with those reported in randomized trials. The data are not yet sufficient to allow for a formal analysis of RFS and OS, and long-term follow-up is required.

Objective: To evaluate the performance of radiomic analysis on contrast-enhanced mammography images to identify different histotypes of breast cancer mainly in order to predict grading, to identify hormone receptors, to discriminate human epidermal growth factor receptor 2 (HER2) and to identify luminal histotype of the breast cancer., Methods: From four Italian centers were recruited 180 malignant lesions and 68 benign lesions. However, only the malignant lesions were considered for the analysis. All patients underwent contrast-enhanced mammography in cranium caudal (CC) and medium lateral oblique (MLO) view. Considering histological findings as the ground truth, four outcomes were considered: (1) G1 + G2 vs. G3; (2) HER2 + vs. HER2 - ; (3) HR + vs. HR - ; and (4) non-luminal vs. luminal A or HR + /HER2-  and luminal B or HR + /HER2 + . For multivariate analysis feature selection, balancing techniques and patter recognition approaches were considered., Results: The univariate findings showed that the diagnostic performance is low for each outcome, while the results of the multivariate analysis showed that better performances can be obtained. In the HER2 + detection, the best performance (73% of accuracy and AUC = 0.77) was obtained using a linear regression model (LRM) with 12 features extracted by MLO view. In the HR + detection, the best performance (77% of accuracy and AUC = 0.80) was obtained using a LRM with 14 features extracted by MLO view. In grading classification, the best performance was obtained by a decision tree trained with three predictors extracted by MLO view reaching an accuracy of 82% on validation set. In the luminal versus non-luminal histotype classification, the best performance was obtained by a bagged tree trained with 15 predictors extracted by CC view reaching an accuracy of 94% on validation set., Conclusions: The results suggest that radiomics analysis can be effectively applied to design a tool to support physician decision making in breast cancer classification. In particular, the classification of luminal versus non-luminal histotypes can be performed with high accuracy., (© 2024. Italian Society of Medical Radiology.)

Objective: The objective of the study was to evaluate the accuracy of radiomics features obtained by MR images to predict Breast Cancer Histological Outcome., Methods: A total of 217 patients with malignant lesions were analysed underwent MRI examinations. Considering histological findings as the ground truth, four different types of findings were used in both univariate and multivariate analyses: (1) G1 + G2 vs G3 classification; (2) presence of human epidermal growth factor receptor 2 (HER2 + vs HER2 -); (3) presence of the hormone receptor (HR + vs HR -); and (4) presence of luminal subtypes of breast cancer., Results: The best accuracy for discriminating HER2 + versus HER2 - breast cancers was obtained considering nine predictors by early phase T1-weighted subtraction images and a decision tree (accuracy of 88% on validation set). The best accuracy for discriminating HR + versus HR - breast cancers was obtained considering nine predictors by T2-weighted subtraction images and a decision tree (accuracy of 90% on validation set). The best accuracy for discriminating G1 + G2 versus G3 breast cancers was obtained considering 16 predictors by early phase T1-weighted subtraction images in a linear regression model with an accuracy of 75%. The best accuracy for discriminating luminal versus non-luminal breast cancers was obtained considering 27 predictors by early phase T1-weighted subtraction images and a decision tree (accuracy of 94% on validation set)., Conclusions: The combination of radiomics analysis and artificial intelligence techniques could be used to support physician decision-making in prediction of Breast Cancer Histological Outcome., (© 2023. Italian Society of Medical Radiology.)

Objective: This study aimed to develop a clinical-radiomic model based on radiomic features extracted from digital breast tomosynthesis (DBT) images and clinical factors that may help to discriminate between benign and malignant breast lesions., Materials and Methods: A total of 150 patients were included in this study. DBT images acquired in the setting of a screening protocol were used. Lesions were delineated by two expert radiologists. Malignity was always confirmed by histopathological data. The data were randomly divided into training and validation set with an 80:20 ratio. A total of 58 radiomic features were extracted from each lesion using the LIFEx Software. Three different key methods of feature selection were implemented in Python: (1) K best (KB), (2) sequential (S), and (3) Random Forrest (RF). A model was therefore produced for each subset of seven variables using a machine-learning algorithm, which exploits the RF classification based on the Gini index., Results: All three clinical-radiomic models show significant differences (p < 0.05) between malignant and benign tumors. The area under the curve (AUC) values of the models obtained with three different feature selection methods were 0.72 [0.64,0.80], 0.72 [0.64,0.80] and 0.74 [0.66,0.82] for KB, SFS, and RF, respectively., Conclusion: The clinical-radiomic models developed by using radiomic features from DBT images showed a good discriminating power and hence may help radiologists in breast cancer tumor diagnoses already at the first screening., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Murtas, Landoni, Ordòñez, Greco, Ferranti, Russo, Perracchio and Vidiri.)

Introduction: In the past decade, a new technique derived from full-field digital mammography has been developed, named contrast-enhanced spectral mammography (CESM). The aim of this study was to define the association between CESM findings and usual prognostic factors, such as estrogen receptors, progesterone receptors, HER2, and Ki67, in order to offer an updated overview of the state of the art for the early differential diagnosis of breast cancer and following personalized treatments., Materials and Methods: According to the PRISMA guidelines, two electronic databases (PubMed and Scopus) were investigated, using the following keywords: breast cancer AND (CESM OR contrast enhanced spectral mammography OR contrast enhanced dual energy mammography) AND (receptors OR prognostic factors OR HER2 OR progesterone OR estrogen OR Ki67). The search was concluded in August 2021. No restriction was applied to publication dates., Results: We obtained 28 articles from the research in PubMed and 114 articles from Scopus. After the removal of six replicas that were counted only once, out of 136 articles, 37 articles were reviews. Eight articles alone have tackled the relation between CESM imaging and ER, PR, HER2, and Ki67. When comparing radiological characterization of the lesions obtained by either CESM or contrast-enhanced MRI, they have a similar association with the proliferation of tumoral cells, as expressed by Ki-67. In CESM-enhanced lesions, the expression was found to be 100% for ER and 77.4% for PR, while moderate or high HER2 positivity was found in lesions with non-mass enhancement and with mass closely associated with a non-mass enhancement component. Conversely, the non-enhancing breast cancer lesions were not associated with any prognostic factor, such as ER, PR, HER2, and Ki67, which may be associated with the probability of showing enhancement. Radiomics on CESM images has the potential for non-invasive characterization of potentially heterogeneous tumors with different hormone receptor status., Conclusions: CESM enhancement is associated with the proliferation of tumoral cells, as well as to the expression of estrogen and progesterone receptors. As CESM is a relatively young imaging technique, a few related works were found; this may be due to the "off-label" modality. In the next few years, the role of CESM in breast cancer diagnostics will be more thoroughly investigated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vasselli, Fabi, Ferranti, Barba, Botti, Vidiri and Tommasin.)

Introduction: To assess the diagnostic accuracy of CESM and 3T MRI compared to full-field digital mammography (FFDM), plus US, in the evaluation of advanced breast lesions. Materials and Methods: Consenting women with suspicious findings underwent FFDM, US, CESM and 3T MRI. Breast lesions were histologically assessed, with histology being the gold standard. Two experienced breast radiologists, blinded to cancer status, read the images. Diagnostic accuracy of (1) CESM as an adjunct to FFDM and US, and (2) 3T MRI as an adjunct to CESM compared to FFDM and US, was assessed. Measures of accuracy were sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). Results: There were 118 patients included along with 142 histologically characterized lesions. K agreement values were 0.69, 0.68, 0.63 and 0.56 for concordance between the gold standard and FFDM, FFDM + US, CESM and MRI, respectively (p < 0.001, for all). K concordance for CESM was 0.81 with FFDM + US and 0.73 with MRI (p value < 0.001 for all). Conclusions: CESM may represent a valuable alternative and/or an integrating technique to MRI in the evaluation of breast cancer patients.

A hypercoagulable state may either underlie or frankly accompany cancer disease at its onset or emerge in course of cancer development. Whichever the case, hypercoagulation may severely limit administration of cancer therapies, impose integrative supporting treatments and finally have an impact on prognosis. Within a flourishing research pipeline, a recent study of stage I-IIA breast cancer patients has allowed the development of a prognostic model including biomarkers of coagulation activation, which efficiently stratified prognosis of patients in the study cohort. We are now validating our risk assessment tool in an independent cohort of 108 patients with locally advanced breast cancer with indication to neo-adjuvant therapy followed by breast surgery. Within this study population, we will use our tool for risk assessment and stratification in reference to 1. pathologic complete response rate at definitive surgery, intended as our primary endpoint, and 2. rate of thromboembolic events, intended as our secondary endpoint. Patients' screening and enrollment procedures are currently in place. The trial will be shortly enriched by experimental tasks centered on next-generation sequencing techniques for identifying additional molecular targets of treatments which may integrate current standards of therapy in high-risk patients.

Results from randomized trials evaluating taxane versus non-taxane containing regimens in adjuvant breast cancer treatment indicate an advantage in DFS and OS for the taxane-arms, but the best schedule of administration, in combination with anthracyclines or in sequence, is still a debated issue, even if the sequential strategy appears to be less toxic. Up to now, the majority of clinical trials employed the "standard" sequence, with anthracycline-based combinations fi rst, followed by taxanes. Few small phase II trials evaluated the reverse sequence, with taxanes administered fi rst, most of them in metastatic or neoadjuvant setting, suggesting efficacy and lower toxicity. An important issue to be considered is the hypothesized differences in the ability of the drugs to induce cross-resistance to each other, as suggested by data of a preclinical study, and from clinical study with a cross-over design; results of these trials suggest that the best strategy would be to administer a taxane prior to an anthracycline, also according to the Norton and Simon hypothesis. Moreover, trials evaluating the best sequence of anthracyclines and taxanes in adjuvant breast cancer setting are of small sample size, and an adequately powered randomized phase III trial is needed before definitive conclusions are reached.

The fundamental imperative of adjuvant treatment of early breast cancer is to improve long-term survival and minimize toxicity. The inclusion of docetaxel in adjuvant chemotherapy regimens has improved patient survival in comparison to anthracycline-containing regimens, even if the incidence of acute side effects has increased in some studies. However, late or persistent toxic effects are becoming more important due to an increasing proportion of patients remaining disease free after treatment for early breast cancer. Several studies have recently reported that docetaxel-containing regimens without anthracyclines are equally active, and have no apparent cardiotoxicity. At present, docetaxel-based combinations represent an appropriate choice in the adjuvant treatment of HER2-negative breast cancer, and several studies are ongoing aiming at a better evaluation of the efficacy of this agent in order to optimize its role.

Purpose: To determine wether primary CEF is effective in locally advanced breast cancer, as measured by response, local recurrences, disease free survival (DFS) and overall survival (OS)., Material and Methods: From 1990 to 1998, 62 patients with stage III disease were enrolled into a prospective study at Regina Elena Institute for Cancer Research, Rome. Inflammatory breast cancer (IBC) was included. Patients received three 21 days cycles of chemotherapy that consisted in epirubicin 50 mg/m2, cyclophosphamide 400 mg/m2, and fluorouracil 500 mg/m2 i.v. on days 1 and 8. G-CSF (300 microg) was given subcutaneously every other day from day 5 to day 17. After primary chemotherapy, whenever possible, mastectomy or conservative surgery was performed. Subsequently responding patients received the same regimen, while non responders were given a non cross resistant chemotherapy. In case of conservative surgery or initial T4 tumor radiation therapy was performed at the end of adjuvant chemotherapy. ER positive patients received tamoxifen 20 mg/d for five years., Results: Seven IIIA patients had a median OS of 43 months (C.I. 95%, 31-55) and DFS of 42 months (C.I. 95%, 16-68), while 15 IBC patients had a median OS of 52 months (C.I. 95%, 52-79) and DFS of 27 months (C.I. 95%, 14-39). Forty IIIB non inflammatory breast cancer patients had a median DFS of 87 months (C.I. 95%, 1-175); median OS was not reached. Ten-year OS was 28.6% for stage IIIA, 50.6% for stage IIIB and 36% for IBC., Conclusion: Primary CEF appear to be an effective treatment. In our study we obtained a good local control and interesting long term data of disease free and overall survival.