Cancer Risk Factors Awareness in Slovenian Adolescents.

Aim: To evaluate Slovenian adolescents' awareness of common cancer risk and protective factors, identifying knowledge gaps to develop targeted health education initiatives.

Methods: A cross-sectional questionnaire survey was conducted among 795 students aged 13 to 19 years in primary and secondary schools in Slovenia. The responses were analysed using descriptive and analytical statistics.

Longitudinal interpretability of deep learning based breast cancer risk prediction.

Deep-learning-based models have achieved state-of-the-art breast cancer risk (BCR) prediction performance. However, these models are highly complex, and the underlying mechanisms of BCR prediction are not fully understood. Key questions include whether these models can detect breast morphologic changes that lead to cancer.

Exploring the impact of BRCA1 and BRCA2 mutation type and location on Olaparib maintenance therapy in platinum-sensitive relapsed ovarian Cancer patients: A single center report.

Objective: In patients with platinum-sensitive relapsed ovarian cancer (PSROC) harboring pathogenic/likely pathogenic variants (PV) in BRCA1 and BRCA2 genes, olaparib maintenance monotherapy (OMT) is a viable option. Our study aimed to evaluate the impact of different BRCA1/2 PV in survival outcomes and safety of OMT in BRCA1/2-mutated PSROC patients, focusing on the type and location of PV.

Methods: We assessed the outcomes of 100 BRCA1/2-mutated PSROC patients treated at our institute, analyzing progression-free survival (PFS) and overall survival (OS).

Breast cancer risk prediction using Tyrer-Cuzick algorithm with an 18-SNPs polygenic risk score in a European population with below-average breast cancer incidence.

Goals: To determine whether an 18 single nucleotide polymorphisms (SNPs) polygenic risk score (PRS18) improves breast cancer (BC) risk prediction for women at above-average risk of BC, aged 40-49, in a Central European population with BC incidence below EU average.

Methods: 502 women aged 40-49 years at the time of BC diagnosis completed a questionnaire on BC risk factors (as per Tyrer-Cuzick algorithm) with data known at age 40 and before BC diagnosis. Blood samples were collected for DNA isolation.

Breast cancer risk assessment and risk distribution in 3,491 Slovenian women invited for screening at the age of 50; a population-based cross-sectional study.

Background: The evidence shows that risk-based strategy could be implemented to avoid unnecessary harm in mammography screening for breast cancer (BC) using age-only criterium. Our study aimed at identifying the uptake of Slovenian women to the BC risk assessment invitation and assessing the number of screening mammographies in case of risk-based screening.

Patients And Methods: A cross-sectional population-based study enrolled 11,898 women at the age of 50, invited to BC screening.

MSH3-related adenomatous polyposis in a patient with the negative family history of colorectal polyps.

Recently, biallelic MSH3 germline pathogenic/likely pathogenic variants have been recognized as a rare cause of adenomatous polyposis. We present a 49-year-old woman who was admitted to our high-risk colorectal cancer clinic after incidental detection of a biallelic MSH3 (likely) pathogenic variant when tested for the germline (likely) pathogenic variants in hereditary breast and ovarian cancer related genes. The focus of this case report is to describe the genotype and phenotype of our patient with MSH3-related adenomatous polyposis.

A Population-Based Study of Patients With Small Cell Carcinoma of the Ovary, Hypercalcemic Type, Encompassing a 30-Year Period.

Context.—: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and lethal tumor, characterized by hypercalcemia and early onset and associated with germline and somatic SMARCA4 variants.

Objective.

Uncertainty estimation for deep learning-based pectoral muscle segmentation via Monte Carlo dropout.

. Deep Learning models are often susceptible to failures after deployment. Knowing when your model is producing inadequate predictions is crucial.

Genotype-first approach to identify associations between CDH1 germline variants and cancer phenotypes: a multicentre study by the European Reference Network on Genetic Tumour Risk Syndromes.

Background: Truncating pathogenic or likely pathogenic variants of CDH1 cause hereditary diffuse gastric cancer (HDGC), a tumour risk syndrome that predisposes carrier individuals to diffuse gastric and lobular breast cancer. Rare CDH1 missense variants are often classified as variants of unknown significance. We conducted a genotype-phenotype analysis in families carrying rare CDH1 variants, comparing cancer spectrum in carriers of pathogenic or likely pathogenic variants (PV/LPV; analysed jointly) or missense variants of unknown significance, assessing the frequency of families with lobular breast cancer among PV/LPV carrier families, and testing the performance of lobular breast cancer-expanded criteria for CDH1 testing.

Medullary Thyroid Carcinoma and Associated Endocrinopathies in Slovenia from 1995 to 2021.

Background: Medullary thyroid cancer (MTC) is a rare endocrine tumour that is sporadic in 75% of cases and occurs as a part of inherited cancer syndromes in approximately 25% of cases. The aim of this study was to determine the frequency and type of pathogenic variants (PVs) in the Slovenian MTC patient population diagnosed between 1995 and 2021 and to elucidate the full range of associated endocrinopathies.

Methods: A retrospective analysis of medical records of 266 MTC patients and their relatives seen in a tertiary centre between 1995 and 2021 was performed.

Identification of Spliceogenic Variants beyond Canonical GT-AG Splice Sites in Hereditary Cancer Genes.

Pathogenic/likely pathogenic variants in susceptibility genes that interrupt RNA splicing are a well-documented mechanism of hereditary cancer syndromes development. However, if RNA studies are not performed, most of the variants beyond the canonical GT-AG splice site are characterized as variants of uncertain significance (VUS). To decrease the VUS burden, we have bioinformatically evaluated all novel VUS detected in 732 consecutive patients tested in the routine genetic counseling process.

BAP1-defficient breast cancer in a patient with BAP1 cancer syndrome.

BAP1 cancer syndrome is a rare and highly penetrant hereditary cancer predisposition. Uveal melanoma, mesothelioma, renal cell carcinoma (RCC) and cutaneous melanoma are considered BAP1 cancer syndrome core cancers, whereas association with breast cancer has previously been suggested but not confirmed so far. In view of BAP1 immunomodulatory functions, BAP1 alterations could prove useful as possible biomarkers of response to immunotherapy in patients with BAP1-associated cancers.

Real-World Data on Detection of Germline and Somatic Pathogenic/Likely Pathogenic Variants in and Other Susceptibility Genes in Ovarian Cancer Patients Using Next Generation Sequencing.

Detection of germline and somatic pathogenic/likely pathogenic variants (PV/LPV) in BRCA genes is at the moment a prerequisite for use of PARP inhibitors in different treatment settings of different tumors. The aim of our study was to determine the most appropriate testing workflow in epithelial ovarian cancer (EOC) patients using germline and tumor genotyping of BRCA and other hereditary breast and/or ovarian cancer (HBOC) susceptibility genes. Consecutive patients with advanced non-mucinous EOC, who responded to platinum-based chemotherapy, were included in the study.

Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review and Individual Patient Data Meta-Analysis.

Purpose: After risk-reducing salpingo-oophorectomy (RRSO), / pathogenic variant (PV) carriers have a residual risk to develop peritoneal carcinomatosis (PC). The etiology of PC is not yet clarified, but may be related to serous tubal intraepithelial carcinoma (STIC), the postulated origin for high-grade serous cancer. In this systematic review and individual patient data meta-analysis, we investigate the risk of PC in women with and without STIC at RRSO.

Quality assured implementation of the Slovenian breast cancer screening programme.

Setting: The organised, population-based breast cancer screening programme in Slovenia began providing biennial mammography screening for women aged 50-69 in 2008. The programme has taken a comprehensive approach to quality assurance as recommended by the European guidelines for quality assurance in breast cancer screening and diagnosis (4th edition), including centralized assessment, training and supervision, and proactive monitoring of performance indicators. This report describes the progress of implementation and rollout from 2003 through 2019.

New Approach for Detection of Normal Alternative Splicing Events and Aberrant Spliceogenic Transcripts with Long-Range PCR and Deep RNA Sequencing.

RNA sequencing is a promising technique for detecting normal and aberrant RNA isoforms. Here, we present a new single-gene, straightforward 1-day hands-on protocol for detection of splicing alterations with deep RNA sequencing from blood. We have validated our method's accuracy by detecting previously published normal splicing isoforms of gene.

Genetic testing results in Slovenian male breast cancer cohort indicate the BRCA2 7806-2A > G founder variant could be associated with higher male breast cancer risk.

Purpose: To analyze the prevalence of pathogenic/likely pathogenic variants (P/LPVs) in BRCA1 and BRCA2 genes in the largest cohort of Slovenian male breast cancer (MBC) patients to date and to explore a possible correlation between the Slovenian founder variant BRCA2:c.7806-2A > G and predisposition to MBC.

Methods: We performed a retrospective analysis of 81 MBC cases who underwent genetic counseling and/or testing between January 1999 and May 2020.

Trends and timing of risk-reducing mastectomy uptake in unaffected BRCA1 and BRCA2 carriers in Slovenia.

Objectives: Risk-reducing mastectomy (RRM) is one of key prevention strategies in female carriers of germline BRCA pathogenic/likely pathogenic variants (PV/LPV). We retrospectively investigated the rate, timing and longitudinal trends of bilateral RRM uptake and the incidence and types of cancers among unaffected BRCA carriers who underwent genetic counseling at the Institute of Oncology Ljubljana in Slovenia.

Materials And Methods: Female BRCA carriers without personal history of cancer were included in the study.

Screening Strategy Modification Based on Personalized Breast Cancer Risk Stratification and its Implementation in the National Guidelines - Pilot Study.

Background: One of the most consistent models for estimating personalized breast cancer (BC) risk is the Tyrer-Cuzick algorithm that is incorporated into the International Breast Cancer Intervention Study (IBIS) software. Our main objective was to provide criteria for the classification of the Slovenian population, which has BC incidence below the European average, into risk groups, and to evaluate the integration of the criteria in Slovenian guidelines. Our main focus was on women age <50 with higher BC risk, since no organized BC screening is available for these women.

Bilateral Disease Common Among Slovenian CHEK2-Positive Breast Cancer Patients.

Background: Currently, data on pathogenic variants in the CHEK2 gene and their impact on cancer risk are lacking. This study aimed to explore the characteristics of breast cancer (BC) patients from families with CHEK2 pathogenic variants in Slovenia.

Methods: In the years 2014 to 2019, CHEK2 pathogenic variants/likely pathogenic variants (PV/LPVs) were found in probands from 50 different families who underwent genetic counseling and testing using a multigene panel at the authors' institution.

Common Susceptibility Loci for Male Breast Cancer.

Background: The etiology of male breast cancer (MBC) is poorly understood. In particular, the extent to which the genetic basis of MBC differs from female breast cancer (FBC) is unknown. A previous genome-wide association study of MBC identified 2 predisposition loci for the disease, both of which were also associated with risk of FBC.

Breast cancer risk based on adapted IBIS prediction model in Slovenian women aged 40-49 years - could it be better?

Background The aim of the study was to assess the proportion of women that would be classified as at above-average risk of breast cancer based on the 10 year-risk prediction of the Slovenian breast cancer incidence rate (S-IBIS) program in two presumably above-average breast cancer risk populations in age group 40-49 years: (i) women referred for any reason to diagnostic breast centres and (ii) women who were diagnosed with breast cancer aged 40-49 years. Breast cancer is the commonest female cancer in Slovenia, with an incidence rate below European average. The Tyrer-Cuzick breast cancer risk assessment algorithm was recently adapted to S-IBIS.