Long term follow-up of women treated for screen detected atypical ductal hyperplasia or lobular neoplasia in a large UK screening centre.

Background: Atypical ductal hyperplasia (ADH) and lobular neoplasia (LN) increase subsequent breast cancer (BC) risk. However, optimal surveillance and risk reduction regimes remain uncertain. We report management and outcomes of women with ADH and LN to provide data on potential screening/prevention strategies.

Are Women's Breast Cancer Risk Appraisals in Line with Updated Clinical Risk Estimates Communicated? Results from a UK Family History Risk and Prevention Clinic.

Background: The incorporation of breast density and a polygenic risk score (PRS) into breast cancer risk prediction models can alter previously communicated risk estimates. Previous research finds that risk communication does not usually change personal risk appraisals. This study aimed to examine how women from the family history risk study appraise their breast cancer risk following communication of an updated risk estimate.

Capability and reliability of deep learning models to make density predictions on low-dose mammograms.

Purpose: Breast density is associated with the risk of developing cancer and can be automatically estimated using deep learning models from digital mammograms. Our aim is to evaluate the capacity and reliability of such models to predict density from low-dose mammograms taken to enable risk estimates for younger women.

Approach: We trained deep learning models on standard-dose and simulated low-dose mammograms.

Buoyancy forcing and the subpolar Atlantic meridional overturning circulation.

The North Atlantic meridional overturning circulation and its variability are examined in terms of the overturning in density space and diapycnal water mass transformation. The magnitude of the mean overturning is similar to the surface water mass transformation, but the density and properties of these waters are modified by diapycnal mixing. Surface waters are progressively densified while circulating cyclonically around the subpolar gyre, with the densest waters and deepest convection occurring in the Labrador Sea and Nordic Seas.

Translabyrinthine resection of NF2 associated vestibular schwannoma with cochlear implant insertion.

The authors present the case of a 24-year-old female with neurofibromatosis type 2. Growth of the left vestibular schwannoma and progressive hearing loss prompted the decision to proceed to translabyrinthine resection with cochlear nerve preservation and cochlear implant insertion. Complete resection with preservation of the facial and cochlear nerves was achieved.

Cochlear Implantation in Neurofibromatosis Type 2: Experience From the UK Neurofibromatosis Type 2 Service.

Objective: To review the outcomes of cochlear implants (CI) in patients with neurofibromatosis type 2 (NF2) in a large cohort, and identify factors associated with poor hearing benefit.

Study Design: Fifteen-year retrospective national observational case series.

Setting: United Kingdom regional NF2 multidisciplinary teams.

Inherited Cancer Genetic Epidemiology to Improve Precision Medicine.

Epidemiology is the study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to the control of health problems [...

No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in and : A Prospective Lynch Syndrome Database Study.

Background: Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance.

The spatial phenotype of genotypically distinct meningiomas demonstrate potential implications of the embryology of the meninges.

Meningiomas are the most common primary brain tumor and their incidence and prevalence is increasing. This review summarizes current evidence regarding the embryogenesis of the human meninges in the context of meningioma pathogenesis and anatomical distribution. Though not mutually exclusive, chromosomal instability and pathogenic variants affecting the long arm of chromosome 22 (22q) result in meningiomas in neural-crest cell-derived meninges, while variants affecting Hedgehog signaling, PI3K signaling, TRAF7, KLF4, and POLR2A result in meningiomas in the mesodermal-derived meninges of the midline and paramedian anterior, central, and ventral posterior skull base.

Beyond Antoni: A Surgeon's Guide to the Vestibular Schwannoma Microenvironment.

 Vestibular schwannomas (VS) are histologically benign tumors arising from cranial nerve VIII. Far from a homogenous proliferation of Schwann cells, mounting evidence has highlighted the complex nature of the inflammatory microenvironment in these tumors.  A review of the literature pertaining to inflammation, inflammatory molecular pathways, and immune-related therapeutic targets in VS was performed.

The inflammatory microenvironment in vestibular schwannoma.

Vestibular schwannomas are tumors arising from the vestibulocochlear nerve at the cerebellopontine angle. Their proximity to eloquent brainstem structures means that the pathology itself and the treatment thereof can be associated with significant morbidity. The vast majority of these tumors are sporadic, with the remainder arising as a result of the genetic syndrome Neurofibromatosis Type 2 or, more rarely, related schwannomatosis.

A case-control evaluation of 143 single nucleotide polymorphisms for breast cancer risk stratification with classical factors and mammographic density.

Panels of single nucleotide polymorphisms (SNPs) stratify risk for breast cancer in women from the general population, but studies are needed assess their use in a fully comprehensive model including classical risk factors, mammographic density and more than 100 SNPs associated with breast cancer. A case-control study was designed (1,668 controls, 405 cases) in women aged 47-73 years attending routine screening in Manchester UK, and enrolled in a wider study to assess methods for risk assessment. Risk from classical questionnaire risk factors was assessed using the Tyrer-Cuzick model; mean percentage visual mammographic density was scored by two independent readers.

Epithelial ovarian cancer risk: A review of the current genetic landscape.

Ovarian cancer is the fourth most common cause of cancer-related death in women in the developed world, and one of the most heritable cancers. One of the most significant risk factors for epithelial ovarian cancer (EOC) is a family history of breast and/or ovarian cancer. Combined risk factors can be used in models to stratify risk of EOC, and aid in decisions regarding risk-reduction strategies.

The association between weight at birth and breast cancer risk revisited using Mendelian randomisation.

Observational studies suggest that higher birth weight (BW) is associated with increased risk of breast cancer in adult life. We conducted a two-sample Mendelian randomisation (MR) study to assess whether this association is causal. Sixty independent single nucleotide polymorphisms (SNPs) known to be associated at P < 5 × 10 with BW were used to construct (1) a 41-SNP instrumental variable (IV) for univariable MR after removing SNPs with pleiotropic associations with other breast cancer risk factors and (2) a 49-SNP IV for multivariable MR after filtering SNPs for data availability.

Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes.

Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families.

Diagnosis of sporadic neurofibromatosis type 2 in the paediatric population.

Objective: Onset of symptoms in severe sporadic neurofibromatosis type 2 (NF2) is typically within childhood; however, there is poor awareness of presenting features in young children, potentially resulting in delayed diagnosis and poorer outcome. We have reviewed presentation of sporadic paediatric NF2 to raise awareness of early features, highlighting those requiring further investigation.

Design: Patients diagnosed with NF2 at age ≤16 and seen between 2012 and 2015 were notified via the British Paediatric Neurology Surveillance Unit or identified through the English NF2 service.

Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting mutations in a Southeast Asian country.

Background: Germline mutations in the 1 and 2 genes have significant clinical implications for both risk-reducing and early surveillance management. The third and most recent revision of the Manchester scoring system (MSS3) used to distinguish patients indicated for germline testing included further adjustments for triple negative breast cancer, high-grade serous ovarian cancer and human epidermal growth factor 2 (HER2) receptor status. This study aims to evaluate the relative effectiveness of MSS3 in a Southeast Asian population.

An update on the diagnosis and treatment of vestibular schwannoma.

Vestibular schwannomas (VS) account for approximately 85% of tumors in the cerebello-pontine angle, with a lifetime incidence of approximately 1 in 1000. Most are sporadic, with approximately 5% related to the tumor predisposition syndrome Neurofibromatosis Type 2 (NF2). The mainstays of management strategies are: observation, surgery, radiosurgery/radiotherapy and, for patients with NF2 and rapidly growing tumors or deteriorating neurologic function the targeted therapy bevacizumab.

Colorectal cancer incidence in carriers subjected to different follow-up protocols: a Prospective Lynch Syndrome Database report.

Background: We have previously reported a high incidence of colorectal cancer (CRC) in carriers of pathogenic variants ) despite follow-up with colonoscopy including polypectomy.

Methods: The cohort included Finnish carriers enrolled in 3-yearly colonoscopy ( = 505; 4625 observation years) and carriers from other countries enrolled in colonoscopy 2-yearly or more frequently ( = 439; 3299 observation years). We examined whether the longer interval between colonoscopies in Finland could explain the high incidence of CRC and whether disease expression correlated with differences in population CRC incidence.

Auditory Brainstem Implantation in Neurofibromatosis Type 2: Experience From the Manchester Programme.

Objective: To describe the experience of auditory brainstem implantation (ABI) in patients with Neurofibromatosis type 2 (NF2).

Study Design: Retrospective case review.

Setting: Tertiary referral centre.