Publications by authors named "Antonis Antoniou"
Introduction: Incorporation of mammographic density to breast cancer risk models could improve risk stratification to tailor screening and prevention strategies according to risk. Robust evaluation of the value of adding mammographic density to models with comprehensive information on questionnaire-based risk factors and polygenic risk score is needed to determine its effectiveness in improving risk stratification of such models.
Methods: We used the Individualized Coherent Absolute Risk Estimator (iCARE) tool for risk model building and validation to incorporate density to a previously validated literature-based model with questionnaire-based risk factors and a 313-variant polygenic risk score (PRS).
Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.
Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.
Background: The BOADICEA model predicts breast cancer risk using cancer family history, epidemiological and genetic data. We evaluated its validity in a large prospective cohort.
Methods: We assessed model calibration, discrimination and risk classification ability in 217,885 women (6,838 incident breast cancers) aged 40-70 years old of self-reported White ethnicity with no previous cancer from the UK Biobank.
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.
Article Synopsis
- NICE recommends additional breast screening and interventions for women in England at above-population risk for breast cancer.
- A review of GP referrals showed up to 20% of women lacked sufficient information for risk assessment, with over 25% assessed as near-population risk.
- Many women may miss out on preventative measures due to current systemic issues, highlighting the need for better data collection and risk assessment processes to address health inequalities.
Purpose: Second primary cancer (SPC) risks after breast cancer (BC) in pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records.
Methods: We followed 25,811 females and 480 males diagnosed with BC and tested for germline PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020.
Population screening for breast cancer (BC) is currently offered in the UK for women aged 50 to 71 with the aim of reducing mortality. There is additional screening within the national programme for women identified as having a very high risk of BC. There is growing interest in further risk stratification in breast screening, which would require a whole population risk assessment and the subsequent offer of screening tailored to the individual's risk.
View Article and Find Full Text PDFBackground: 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
- Multifactorial cancer risk prediction tools like CanRisk are being increasingly used in healthcare, but effectively communicating this risk information is challenging for healthcare professionals.
- A 13-month co-design process involved patients, the public, and healthcare professionals to develop a new CanRisk report after receiving feedback on the original.
- The revised report presents key information for individuals and healthcare professionals, including summaries, explanatory text, and visual aids, enhancing communication around cancer risk management.
Background: The clinical validity of the multifactorial BOADICEA model for epithelial tubo-ovarian cancer (EOC) risk prediction has not been assessed in a large sample size or over a longer term.
Methods: We evaluated the model discrimination and calibration in the UK Biobank cohort comprising 199,429 women (733 incident EOCs) of European ancestry without previous cancer history. We predicted 10-year EOC risk incorporating data on questionnaire-based risk factors (QRFs), family history, a 36-SNP polygenic risk score and pathogenic variants (PV) in six EOC susceptibility genes (BRCA1, BRCA2, RAD51C, RAD51D, BRIP1 and PALB2).
Article Synopsis
- Clinical genetic testing helps find cancer risks by identifying gene changes, but some of these changes are confusing because we don't know what they mean (called VUS).
- Researchers studied a huge number of breast cancer patients and healthy people to understand these confusing gene changes better.
- They found that their method of analyzing data closely matches what other experts say about which gene changes are harmless or harmful, giving more information about 785 unclear changes.
Common genetic variation throughout the genome together with rare coding variants identified to date explain about a half of the inherited genetic component of epithelial ovarian cancer risk. It is likely that rare variation in the non-coding genome will explain some of the unexplained heritability, but identifying such variants is challenging. The primary problem is lack of statistical power to identifying individual risk variants by association as power is a function of sample size, effect size and allele frequency.
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- * Analysis of data from over 55,000 breast cancer patients showed that co-observation of variants in BRCA1, BRCA2, and PALB2 with other breast cancer genes occurred less frequently than expected, suggesting a potential correlation with pathogenicity.
- * The findings indicate that identifying a variant of uncertain significance alongside a known pathogenic variant supports evidence against the variant's pathogenicity, which could improve variant classification in clinical settings and for other genetic conditions.
Breast cancer risks in older pathogenic variant carriers are understudied. Recent studies show a marked decline in the relative risk at older ages. We used data from two large studies to update the breast cancer risks in the BOADICEA model for carriers 60 years and older.
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- Scientists looked at the timing of when girls start their periods (called menarche) and how it can affect their health later in life.
- They studied about 800,000 women and found over a thousand genetic signals that influence when menstruation starts.
- Some women have a much higher chance of starting their periods too early or too late based on their genetic makeup, suggesting that genes play a big role in this process!
Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population setting to inform the implementation of risk-stratified screening. Recruited females aged 40-69 unaffected by breast cancer, with a previous mammogram, underwent multifactorial breast cancer risk assessment.
View Article and Find Full Text PDFBackground: The CanRisk tool, which operationalises the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) is used by Clinical Geneticists, Genetic Counsellors, Breast Oncologists, Surgeons and Family History Nurses for breast cancer risk assessments both nationally and internationally. There are currently no guidelines with respect to the day-to-day clinical application of CanRisk and differing inputs to the model can result in different recommendations for practice.
Methods: To address this gap, the UK Cancer Genetics Group in collaboration with the Association of Breast Surgery and the CanGene-CanVar programme held a workshop on 16 of May 2023, with the aim of establishing best practice guidelines.
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.
Background: Second primary cancers (SPCs) after breast cancer (BC) present an increasing public health burden, with little existing research on socio-demographic, tumour, and treatment effects. We addressed this in the largest BC survivor cohort to date, using a novel linkage of National Disease Registration Service datasets.
Methods: The cohort included 581,403 female and 3562 male BC survivors diagnosed between 1995 and 2019.
Background: Menopausal hormone therapy (MHT) can alleviate menopausal symptoms but has been associated with an increased risk of breast cancer. MHT prescription should be preceded by individualised risk/benefit evaluation; however, data outlining the impact of family history alongside different MHT therapeutic approaches are lacking.
Aim: To quantify the risks associated with MHT use in women with varying breast cancer family histories of developing and dying from breast cancer.
Purpose: Mammographic density phenotypes, adjusted for age and body mass index (BMI), are strong predictors of breast cancer risk. BMI is associated with mammographic density measures, but the role of circulating sex hormone concentrations is less clear. We investigated the relationship between BMI, circulating sex hormone concentrations, and mammographic density phenotypes using Mendelian randomization (MR).
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