BRCA guidelines

BACKGROUND: Hereditary breast/ovarian cancer is associated with BRCA gene mutations. As large volumes of clinical data on BRCA variants are continuously updated, their clinical interpretation may change, leading to their reclassification. This study analyzed the class and proportion of the changed clinical interpretations of BRCA variants to validate the need for periodic reviews of these variants. METHODS: This retrospective study reinterpreted previously reported BRCA1 and BRCA2 exon variants according to the 2015 American College of Medical Genetics and Genomics guidelines and the clinical significance of the recent public genomic database...

PURPOSE: Carriers of pathogenic variants in BRCA1/2 have an elevated lifetime cancer risk warranting high-risk screening and risk-reducing procedures for early detection and prevention. We report on prevention practices among women with pathogenic BRCA variants in order to document follow through with NCCN recommendations and to identify barriers to guideline-recommended care. METHODS: Our cohort included women who had genetic testing through a cancer genetic clinic and completed a 54-item questionnaire to measure socio-demographics, medical history, rates of cancer screening and risk-reducing surgery, disclosure of test results, and cancer worry...

Endometrial cancer (EC) incidence and mortality rates have been increasing, particularly among young females. Although more than 90% of ECs are sporadic, 5-10% are hereditary, a majority of which occurs within Hereditary Non-Polyposis Colorectal Cancer syndrome (HNPCC) or Lynch syndrome. The traditional histopathological classification differentiates EC between two main groups: type I (or endometrioid) and type II (including all other histopathological subtypes). However, this classification lacks reproducibility and does not account for the emerging molecular heterogeneity...

BACKGROUND: A detailed understanding of the genetic basis of cancer is of great interest to public health monitoring programs. Although many studies have been conducted in Brazil, a global view on the molecular profile related to hereditary breast and ovarian cancer (HBOC) in this large and heterogeneous population is lacking. METHODS: A systematic review following the PRISMA guidelines was conducted in three electronic databases (PubMed, BIREME and SciELO). Brazilian studies covering molecular analysis of genes related to HBOC, published until December 2023, were considered...

BACKGROUND: Assessment of homologous recombinant deficient (HRD) phenotypes is key for managing Poly (ADP-ribose) polymerase inhibitor (PARPi) treatment. To accommodate the need for a validated HRD platform and enhance targeted treatment of ovarian cancer patients, a Nordic core facility for the myChoice® CDx platform was established in Denmark. MATERIALS AND METHODS: Comparative calculations and statistics are based on information from test requisitions and results (Genome Instability Score [GIS], BRCA status and combined HRD status) obtained from ovarian and breast cancer samples submitted for HRD-testing by myChoice® CDx through the Nordic core facility in the 2-year period...

INTRODUCTION: Breast cancer is the most common cancer among Indian females. There is limited data on germline profiling of breast cancer patients from India. OBJECTIVE: The objective of the current study was to analyse the frequency and spectrum of germline variant profiles and clinicopathological characteristics of breast cancer patients referred to our Familial Cancer Clinic (FCC). MATERIALS AND METHODS: It is a single-centre audit of patients with a confirmed diagnosis of breast carcinoma referred to our FCC from January 2017 to 2020...

INTRODUCTION: DNA damage repair genes are altered in 20-35% of metastatic castration-resistant prostate cancer (mCRPC). Poly-ADP (Adénosine Diphosphate)-ribose polymerase inhibitors (PARPi) showed significant activity for these selected tumors, especially with homologous recombination repair (HRR) deficiency. These alterations could also predict platinum sensitivity. Although carboplatin was inconclusive in unselected mCRPC, the literature suggests an anti-tumoral activity in mCRPC with HHR gene alterations...

Advancements in digital pathology and computing resources have made a significant impact in the field of computational pathology for breast cancer diagnosis and treatment. However, access to high-quality labeled histopathological images of breast cancer is a big challenge that limits the development of accurate and robust deep learning models. In this scoping review, we identified the publicly available datasets of breast H&E-stained whole-slide images (WSIs) that can be used to develop deep learning algorithms...

PURPOSE: A semi-annual surveillance scheme from age 25 to 30 years is offered to BRCA1/BRCA2 pathogenic sequence variants (PSVs) carriers for early detection of breast cancer (BC). There is a paucity of data on the yield of adhering to this scheme beyond 70 years of age. METHODS: Female BRCA1/BRCA2 PSV carriers followed at the Meirav high-risk clinic, Sheba Medical center, Israel were eligible. Type and frequencies if use of Imaging modalities, breast biopsies and histological outcomes for participants after age 70 years were retrieved and analyzed...

PURPOSE: Current guidelines recommend combination chemotherapy for treatment of patients with unfavorable cancer of unknown primary (CUP). Biomarker-guided targeted therapies may offer additional benefit. Data on the feasibility and effectiveness of comprehensive genomic biomarker profiling of CUP in a standard clinical practice setting are limited. METHODS: This analysis included 156 patients with confirmed unfavorable CUP diagnosis according to ESMO guidelines, who were treated at the West German Cancer Center, Essen, Germany, from 2015 to 2021...

BACKGROUND: Pathogenic variants in BRCA genes play a crucial role in the pathogenesis of ovarian cancer. Intronic variants of uncertain significance (VUS) may contribute to pathogenicity by affecting splicing. Currently, the significance of many intronic variants in BRCA has not been clarified, impacting patient treatment strategies and the management of familial cases. METHOD: A retrospective study was conducted to analyze BRCA intronic VUS in a cohort of 707 unrelated ovarian cancer patients at a single institution from 2018 to 2023...

BACKGROUND: Germline BRCA mutations (gBRCAm) occur in 4%-8% patients with metastatic pancreatic cancer (mPC); guidelines recommend platinum-based chemotherapies and olaparib maintenance in this population. We evaluated, through modeling, the role of treatments and gBRCA testing on health outcomes of mPC patients. METHODS: A decision tree/partitioned survival model was developed to assess lifetime health outcomes for four strategies: 1) no testing; 2) early testing/no olaparib maintenance; 3) early testing (i...

BACKGROUND: Care for families affected by Familial Breast and Ovarian Cancer (FBOC) is challenging as a broad range of professions and specialties are involved. The aim was to review management and outcomes for a cohort of women at high risk for familial breast and ovarian cancer. METHODS: Ten-year retrospective follow-up study of individuals in Southern New Zealand  assessed by Genetic Health Service New Zealand to be high risk for FBOC and without a personal cancer diagnosis at time of consultation...

BACKGROUND: Hereditary breast and ovarian cancers (HBOCs) pose significant health risks worldwide and are mitigated by prophylactic interventions. However, a meta-analysis of their efficacy and the impact of different genetic variants on their effectiveness is lacking. METHODS: A systematic review and meta-analysis were conducted, adhering to Cochrane guidelines. The review encompassed studies that involved prophylactic interventions for healthy women with BRCA variants, focusing on cancer incidence and mortality outcomes...

OBJECTIVES: Breast oncology genetics emerged almost 30 years ago with the discovery of the BRCA1 and BRCA2 genes. The evolution of analytical practices has progressively allowed access to tests whose results now have a considerable impact on the management of both female and male breast cancers.The Sénologie Commission of the Collège National des Gynécologues et Obstétriciens Français (CNGOF) asked five specialists in breast surgery, oncology and oncological genetics to draw up a summary of the oncogenetic testing criteria used and the clinical implications for the female and male population of the test results, with or without an identified causal variant...

Context : Several recent randomized controlled trials (RCTs) have reported on the survival benefits of poly (ADP-ribose) polymerase inhibitors (PARPi) compared to standard-of-care (SOC) treatment (enzalutamide, abiraterone, or docetaxel) in patients with metastatic castration-resistant prostate cancer (mCRPC). However, there is a limited integrated analysis of high-quality evidence comparing the efficacy and safety of PARPi and SOC treatments in this context. Objective : This study aims to comprehensively analyze the survival benefits and adverse events associated with PARPi and SOC treatments through a head-to-head meta-analysis in mCRPC...

BACKGROUND: This paper explores and discusses local challenges oncologists face for diagnosing and managing breast cancer patients with BRCA gene mutations in Jordan. METHODS: A task force involving key opinion leaders, experts in the management of breast cancer, and stakeholders in healthcare systems where genetic testing is available in Jordan discussed current evidence and local real-life practice. The task force then formulated recommendations to achieve better patient outcomes and satisfaction based on evidence-based medicine and their clinical experience in BRCA-mutated breast cancer management...

BACKGROUND/AIM: The role of postoperative radiotherapy (RT) combined with chemotherapy (CT) for lymph node-positive (LN+) triple-negative breast cancer (TNBC) remains controversial. SUV39H1-mediated epigenetic regulation is associated with cancer cell migration, invasion, metastasis, and treatment resistance. This study aims to identify the role of SUV39H1 in TNBCs. MATERIALS AND METHODS: Overall, 498 TNBCs with SUV39H1 RNA-seq profiles were retrieved from TCGA-BRCA and analyzed; the X-tile algorithm was used to stratify the population into low, intermediate, and high SUV39H1...

Pathogenic variants (PVs) in BRCA1 and BRCA2 increase the lifetime risks of breast and ovarian cancer. Guidelines recommend breast screening (magnetic resonance imaging (MRI) and mammogram) or risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO). We sought to (1) characterize the population of BRCA1/2 PV carriers in Newfoundland and Labrador (NL), (2) evaluate risk-reducing interventions, and (3) identify factors influencing screening and prevention adherence. We conducted a retrospective study from a population-based provincial cohort of BRCA1/2 PV carriers...

BACKGROUND: Numerous reviews of the epidemiology and risk factors for breast cancer have been published previously which heighted different directions of breast cancer. AIM: The present review examined the likelihood that incidence, prevalence, and particular risk factors might vary by geographic region and possibly by food and cultural practices as well. METHODS: A systematic review (2017-2022) was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, reporting on epidemiological and risk factor reports from different world regions...