A primary luminal/HER2 negative breast cancer patient with mismatch repair deficiency

: Here, we present the case of a 47-year-old woman diagnosed with luminal B breast cancer subtype and provide an in-depth analysis of her gene mutations, chromosomal alterations, mRNA and protein expression changes. We found a point mutation in the FGFR2 gene, which is potentially hyper-activating the receptor function, along with over-expression of its ligand FGF20 due to genomic amplification. The patient also harbors somatic and germline mutations in some mismatch repair (MMR) genes, with a strong MMR mutational signature. The patient displays high microsatellite instability (MSI) and tumor mutational burden (TMB) status and increased levels of CTLA-4 and PD-1 expression. Altogether, these data strongly implicate that aberrant FGFR signaling, and defective MMR system might be involved in the development of this breast tumor. In addition, high MSI and TMB in the context of CTLA-4 and PD-L1 positivity, suggest the potential benefit of immune checkpoint inhibitors. Accurate characterization of molecular subtypes, based on gene mutational and expression profiling analyses, will be certainly helpful for individualized treatment and targeted therapy of breast cancer patients, especially for those subtypes with adverse outcome

The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies

Immune checkpoint inhibitors (ICIs) have a modest clinical activity when administered as monotherapy against breast cancer (BC), the most common malignancy in women. Novel combinatorial strategies are currently being investigated to overcome resistance to ICIs and promote antitumor immune responses in a greater proportion of BC patients. Recent studies have shown that the BC abnormal vasculature is associated with immune suppression in patients, and hampers both drug delivery and immune effector cell trafficking to tumor nests. Thus, strategies directed at normalizing (i.e., at remodeling and stabilizing) the immature, abnormal tumor vessels are receiving much attention. In particular, the combination of ICIs with tumor vessel normalizing agents is thought to hold great promise for the treatment of BC patients. Indeed, a compelling body of evidence indicates that the addition of low doses of antiangiogenic drugs to ICIs substantially improves antitumor immunity. In this review, we outline the impact that the reciprocal interactions occurring between tumor angiogenesis and immune cells have on the immune evasion and clinical progression of BC. In addition, we overview preclinical and clinical studies that are presently evaluating the therapeutic effectiveness of combining ICIs with antiangiogenic drugs in BC patients

Prognostic significance of adiponectin levels in non-metastatic colorectal cancer

Circulating adiponectin levels are inversely correlated with the risk of colorectal cancer (CRC). This study was designed to evaluate the association between adiponectin levels and the clinicopathological variables of CRC and to analyze the possible prognostic value of adiponectin in predicting relapse-free survival

A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient

: Triple-negative breast cancer (TNBC) is the most aggressive subtype of mammary carcinoma. Here, we describe a case of an 81-year-old female diagnosed with ductal triple negative breast cancer with a germline pathogenic variant in BReast CAncer gene2 (BRCA2). Genetic testing also revealed the presence of four somatic mutations in the ephrin type-A receptor 3 (EphA3), TP53, BRCA1-associated protein (BAP1), and MYB genes. The BRCA2, TP53, and BAP1 gene mutations are highly predictive of a defective homologous recombination repair system and subsequent chromosomal instability in this patient. Coherently, the patient displayed a strong homologous recombination deficiency signature and high tumor mutational burden status, which are generally associated with increased probability of immune neoantigens formation and presentation, and with tumor immunogenicity. Analysis of immune checkpoint revealed high expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), programmed death 1 (PD1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), suggesting that the patient might likely benefit from immunotherapies. Altogether, these findings support an unveiled link between BRCA2 inactivation, HR deficiency and increased expression of immune checkpoints in TNBC. This clinical case highlights the importance of screening TNBC patients for genetic mutations and TMB biomarkers in order to predict the potential efficacy of immunotherapy

L’inconsistenza della diagnosi di cancro duttale in situ

Background: Classifying ductal carcinoma in situ (DCIS) remains problematical for interpretation of specified histological features and field selection where morphology is heterogeneous. Emphasis is placed on the role of intraductal proliferative lesions as risk factors of variable magnitude in subsequent development of invasive breast carcinoma. The present study is designed to investigate the relative contribution of diagnostic and treatment paradigms on the lack of consistency in the analysis of these lesions. Materials and methods: A cohort of in situ lesions of the breast was reviewed according to ductal intraepithelial neoplasia (DIN) classification adopted by the World Health Organization (WHO). In this retrospective study 458 patients with DIN diagnosed by core needle biopsy had undergone conservative or radical surgical treatment and SLNB in cases of DIN1C-DIN3. Results: Breast conservative surgery was the definitive treatment in 80% of cases. All the SLNs sampled showed 1.2 % (4/336) positivity of metastatic or micrometastatic nodal involvement by H&E stain while the IHC assessment for cytokeratin showed 4.5% (15/336) positivity. Conclusions: The widely recognised variation in the growth pattern of DCIS makes difficult to identify uniform indications for clinical procedure. Although the incidence of metastases in patient with initial diagnosis of DIN is considered to be low, SLNB remains an attractive option to guarantee oncological safety. In patients at high risk occult invasion does occur and without lymphatic analysis, undertreatment is possible

Assessing Patient Organization Participation in Health Policy: A Comparative Study in France and Italy

Abstract Background: Even though there are many patient organizations across Europe, their role in impacting health policy decisions and reforms has not been well documented. In line with this, the present study endeavours to fill this gap in the international literature. To this end, it aims to validate further a previously developed instrument (the Health Democracy Index - HDI) measuring patient organization participation in health policy decision-making. In addition, by utilizing this tool, it aims to provide a snapshot of the degree and impact of cancer patient organization (CPO) participation in Italy and France. Methods: A convenient sample of 188 members of CPOs participated in the study (95 respondents from 10 CPOs in Italy and 93 from 12 CPOs in France). Participants completed online a self-reported questionnaire, encompassing the 9-item index and questions enquiring about the type and impact of participation in various facets of health policy decisionmaking. The psychometric properties of the scale were explored by performing factor analysis (construct validity) and by computing Cronbach α (internal consistency). Results: Findings indicate that the index has good internal consistency and the construct it taps is unidimensional. The degree and impact of CPO participation in health policy decision-making were found to be low in both countries; however in Italy they were comparatively lower than in France. Conclusion: In conclusion, the HDI can be effectively used in international policy and research contexts. CPOs participation is low in Italy and France and concerted efforts should be made on upgrading their role in health policy decision-making

Linear Accelerator Test Facility at LNF Conceptual Design Report

Test beam and irradiation facilities are the key enabling infrastructures for research in high energy physics (HEP) and astro-particles. In the last 11 years the Beam-Test Facility (BTF) of the DA{\Phi}NE accelerator complex in the Frascati laboratory has gained an important role in the European infrastructures devoted to the development and testing of particle detectors. At the same time the BTF operation has been largely shadowed, in terms of resources, by the running of the DA{\Phi}NE electron-positron collider. The present proposal is aimed at improving the present performance of the facility from two different points of view: extending the range of application for the LINAC beam extracted to the BTF lines, in particular in the (in some sense opposite) directions of hosting fundamental physics and providing electron irradiation also for industrial users; extending the life of the LINAC beyond or independently from its use as injector of the DA{\Phi}NE collider, as it is also a key element of the electron/positron beam facility. The main lines of these two developments can be identified as: consolidation of the LINAC infrastructure, in order to guarantee a stable operation in the longer term; upgrade of the LINAC energy, in order to increase the facility capability (especially for the almost unique extracted positron beam); doubling of the BTF beam-lines, in order to cope with the signicant increase of users due to the much wider range of applications.Comment: 71 page

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Comparative study of oncoplastic versus non-oncoplastic breast conserving surgery in a group of 211 breast cancer patients

Breast conserving surgery (BCS) followed by radiotherapy is the standard of care for most patients with early breast cancers; however, the aesthetic outcomes of this procedure is not always desirable. Oncoplastic breast surgery is an innovative approach that aims at the safe and effective treatment of the cancerous lesion while achieving the best possible aesthetic outcome. The aim of this study was to evaluate and compare oncoplastic and non-oncoplastic procedures

Role of breast-conserving surgery on the National Health System economy from and to SARS-COVID-19 era

Day surgery breast-conserving surgery (DS-BCS) is a surgical approach applied in many specialized breast surgery departments. This study demonstrates the benefits of this approach from the perspectives of patients and of the Hospital/National Health System compared to ordinary breast-conserving surgery (ORD-BCS) under general anesthetic. A comparison of costs and diagnosis-related group (DRG) reimbursement demonstrated improved cost-effectiveness in DS-BCS compared to ORD-BCS