Publications by authors named "Lalloo F"
Objective: In England, through the Genomic Medicine Service Alliances (GMSAs), a national transformation project aims to embed robust pathways to deliver universal Lynch syndrome (LS) testing for patients with colorectal and endometrial cancers. Prior to commencement of the project, there was evidence of variation and low testing levels in eligible patients which is consistent with other health systems; however, we believe this is amenable to systematic improvement with responsibility for testing delivery by local cancer teams supported by regional infrastructure.
Methods And Analysis: A project team and national oversight group was formed in May 2021 with membership including 21×cancer alliances, 7×GMSAs, charities and other stakeholders who agreed key performance indicators.
Purpose: To assess the contribution of germline pathogenic variants (PVs) in population-based series of breast cancers and the best strategy to improve detection rates.
Methods: Three cohort studies were utilized, including a hospital-based series identified from new UK mainstream testing criteria (group-1), offering testing to all women (group-2-BReast CAncer [BRCA]-DIRECT), and a Greater Manchester cohort study recruited from the mammography screening population (group-3-Predicting Risk of Cancer at Screening). DNA samples from women with breast cancer were sequenced for PVs in , , and Partner and Localiser of BRCA2 ().
Article Synopsis
- Carriers of BRCA1/2 pathogenic variants were studied to determine their risk of developing cancers during childhood, adolescence, and young adulthood (CAYA).
- Analysis of data from over 47,000 individuals revealed that while young women with BRCA1/2 mutations had a significantly increased risk of breast cancer in their 20s, no increased risk was found for other types of CAYA cancers.
- The study concluded that there's little evidence to support routine genetic testing for children of BRCA1/2 carriers or for young cancer patients, as the overall cancer risk appears low aside from breast cancer in young women.
Background: For female patients with Lynch syndrome (LS), endometrial cancer (EC) is often their first cancer diagnosis. A testing pathway of somatic tumour testing triage followed by germline mismatch repair (MMR) gene testing is an effective way of identifying the estimated 3% of EC caused by LS.
Methods: A retrospective national population-based observational study was conducted using comprehensive national data collections of functional, somatic and germline MMR tests available via the English National Cancer Registration Dataset.
Article Synopsis
- Craniopharyngiomas are usually benign tumors located in the sellar and suprasellar regions, but rare instances of ectopic tumors can occur, particularly associated with familial adenomatous polyposis (FAP).
- The text discusses a case of an ectopic cerebellopontine angle (CPA) craniopharyngioma in a patient with FAP, marking it as the fifth such documented case.
- This case underlines the importance of considering craniopharyngioma in differential diagnoses for CPA tumors, especially in patients with FAP, suggesting a potential link to genetic mutations.
Background: Lynch syndrome is an inherited condition which leads to an increased risk of colorectal, endometrial and ovarian cancer. Risk-reducing surgery is generally recommended to manage the risk of gynaecological cancer once childbearing is completed. The value of gynaecological colonoscopic surveillance as an interim measure or instead of risk-reducing surgery is uncertain.
View Article and Find Full Text PDFPurpose: To compare student performance, examiner perceptions and cost of GPT-assisted (generative pretrained transformer-assisted) clinical and professional skills assessment (CPSAs) items against items created using standard methods.
Methods: We conducted a prospective, controlled, double-blinded comparison of CPSA items developed using GPT-assistance with those created through standard methods. Two sets of six practical cases were developed for a formative assessment sat by final year medical students.
Purpose: The prevalence of germline pathogenic variants (PVs) in homologous recombination repair (HRR) and Lynch syndrome (LS) genes in ovarian cancer (OC) is uncertain.
Methods: An observational study reporting the detection rate of germline PVs in HRR and LS genes in all OC cases tested in the North West Genomic Laboratory Hub between September 1996 and May 2024. Effect sizes are reported using odds ratios (ORs) and 95% confidence intervals (95% CI) for unselected cases tested between April 2021 and May 2024 versus 50,703 controls from the Breast Cancer Risk after Diagnostic Gene Sequencing study.
Purpose: The identification of germline BRCA1/BRCA2 pathogenic variants (PV) infer high remaining lifetime breast/ovarian cancer risks, but there is paucity of studies assessing breast cancer risk after ovarian cancer diagnosis.
Methods: We reviewed the history of breast cancer in 895 PV heterozygotes (BRCA1 = 541). Cumulative annual breast cancer incidence was assessed at 2, 5, 10, and >10 years after ovarian cancer diagnosis date.
Article Synopsis
- The study checked how well the BOADICEA model predicts breast cancer risk for people who carry certain gene changes (called pathogenic variants).
- They looked at information from a group of over 1,600 participants and found that the model worked really well, especially when considering family history and other risk factors.
- The results can help doctors and patients make better choices about cancer management, and the model can be accessed for free on the CanRisk website.
Article Synopsis
- This study investigates the role of inversions—structural variants that involve the rearrangement of DNA—in genetic diseases, using data from 33,924 families involved in the 100,000 Genomes Project.
- Researchers identified 47 ultra-rare rearrangements, including de novo inversions, in genes linked to disease, with analyses correlating genetic findings to clinical outcomes in some cases, including a specific diagnosis for three family members.
- The findings suggest that while inversions are less common in genetic diseases compared to other structural variants, they can significantly contribute to the etiology in approximately 1 in 750 families with rare conditions.
Article Synopsis
- Male breast cancer (MBC) is relatively rare, with 1 in 1000 men affected, and shows a higher likelihood of genetic risk factors compared to female breast cancer.
- The study analyzed germline testing for high-risk gene variants across 204 families with at least one MBC case, finding that 25% had pathogenic variants, particularly linked to specific genes.
- Results indicated that higher scores on the Manchester Scoring System correlate with a higher detection rate of these variants, suggesting it is a useful tool for assessing genetic risk in such families.
In the 33 years since the first diagnostic cancer predisposition gene (CPG) tests in the Manchester Centre for Genomic Medicine, there has been substantial changes in the identification of index cases and cascade testing for at-risk family members. National guidelines in England and Wales are usually determined from the National Institute of healthcare Evidence and these have impacted on the thresholds for testing BRCA1/2 in Hereditary Breast Ovarian Cancer (HBOC) and in determining that all cases of colorectal and endometrial cancer should undergo screening for Lynch syndrome. Gaps for testing other CPGs relevant to HBOC have been filled by the UK Cancer Genetics Group and CanGene-CanVar project (web ref.
View Article and Find Full Text PDFBackground: The identification of germline pathogenic gene variants (PGVs) in triple negative breast cancer (TNBC) is important to inform further primary cancer risk reduction and TNBC treatment strategies. We therefore investigated the contribution of breast cancer associated PGVs to familial and isolated invasive TNBC.
Methods: Outcomes of germline , and _c.
Background: Lynch syndrome is a hereditary cancer disease resulting in an increased risk of colorectal cancer. Herein, findings are reported from an emergency clinical service implemented during the COVID-19 pandemic utilizing faecal immunochemical testing ('FIT') in Lynch syndrome patients to prioritize colonoscopy while endoscopy services were limited.
Methods: An emergency service protocol was designed to improve colonoscopic surveillance access throughout the COVID-19 pandemic in England for people with Lynch syndrome when services were extremely restricted (1 March 2020 to 31 March 2021) and promoted by the English National Health Service.
BRCA1-associated protein-1 (BAP1) is a recognised tumour suppressor gene. Germline BAP1 pathogenic/likely pathogenic variants are associated with predisposition to multiple tumours, including uveal melanoma, malignant pleural and peritoneal mesothelioma, renal cell carcinoma and specific non-malignant neoplasms of the skin, as part of the autosomal dominant BAP1-tumour predisposition syndrome. The overall lifetime risk for BAP1 carriers to develop at least one BAP1-associated tumour is up to 85%, although due to ascertainment bias, current estimates of risk are likely to be overestimated.
View Article and Find Full Text PDFArticle Synopsis
- The study examines the relationship between height, BMI, and weight gain with breast cancer risk in women who carry BRCA1 or BRCA2 gene variants, unlike previous research that focused on the general population.
- An analysis of 8,091 BRCA1/2 variant carriers found that taller height increases the risk of premenopausal breast cancer for BRCA2 carriers, while higher BMI in young adulthood is linked to lower risk for both BRCA1 and BRCA2 carriers.
- The findings suggest that higher BMI and weight gain are related to increased postmenopausal breast cancer risk for BRCA1 carriers, indicating that body measurements impact breast cancer risk similarly in these variant carriers as
Article Synopsis
- The Prospective Lynch Syndrome Database (PLSD) gathers data on individuals with MMR variants to study cancer diagnosis and treatment outcomes, focusing on a newly expanded cohort.
- The study includes over 8,500 patients from 25 countries, analyzing cancer incidence, mortality rates up to age 75, and survival rates after diagnosis.
- Findings reveal that while gynecological cancers have high incidence rates among carriers, non-colorectal cancers lead to more deaths, highlighting the need for improved care for these patients.
Article Synopsis
- A study evaluated the PREDICT v 2.2 tool for predicting the prognosis of breast cancer in patients with BRCA1 and BRCA2 gene variants, using data from over 5,400 carriers across two major cancer research consortia.
- The PREDICT model showed reasonable effectiveness in distinguishing high-mortality groups for estrogen receptor (ER)-negative breast cancer in BRCA1 carriers, while for BRCA2 carriers, its accuracy was lower and fluctuated based on tumor characteristics.
- The findings suggest that while PREDICT can aid in management of breast cancer patients, adjustments for BRCA2 status and tumor features are necessary to improve prognosis estimates, particularly for ER-positive cases.
Article Synopsis
- The study aimed to explore the occurrence of germline pathogenic variants (PVs) in women diagnosed with bilateral breast cancer.
- A total of 764 women underwent testing for specific variants, revealing varying detection rates, particularly higher in triple-negative and specific ER+HER2 cancers.
- Results indicate that the estrogen receptor (ER) status of the first breast cancer significantly predicts the ER status of the second tumor, especially in patients with certain PVs.