A Cohort Study of Hereditary Ovarian Cancer Risk Prediction Models and Pathogenesis Exploration

Ovarian Neoplasms

Ovarian Neoplasms — a type of gynecological cancer.

Enhancing the BOADICEA cancer risk prediction model to incorporate new data on RAD51C , RAD51D , BARD1 updates to tumour pathology and cancer incidence

Background BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) for breast cancer and the epithelial tubo-ovarian cancer (EOC) models included in the CanRisk tool ( www.canrisk.org ) provide future cancer risks based on pathogenic variants in cancer-susceptibility genes, polygenic risk scores, breast density, questionnaire-based risk factors and family history. Here, we extend the models to include the effects of pathogenic variants in recently established breast cancer and EOC susceptibility genes, up-to-date age-specific pathology distributions and continuous risk factors. Methods BOADICEA was extended to further incorporate the associations of pathogenic variants in BARD1 , RAD51C and RAD51D with breast cancer risk. The EOC model was extended to include the association of PALB2 pathogenic variants with EOC risk. Age-specific distributions of oestrogen-receptor-negative and triple-negative breast cancer status for pathogenic variant carriers in these genes and CHEK2 and ATM were also incorporated. A novel method to include continuous risk factors was developed, exemplified by including adult height as continuous. Results BARD1 , RAD51C and RAD51D explain 0.31% of the breast cancer polygenic variance. When incorporated into the multifactorial model, 34%–44% of these carriers would be reclassified to the near-population and 15%–22% to the high-risk categories based on the UK National Institute for Health and Care Excellence guidelines. Under the EOC multifactorial model, 62%, 35% and 3% of PALB2 carriers have lifetime EOC risks of <5%, 5%–10% and >10%, respectively. Including height as continuous, increased the breast cancer relative risk variance from 0.002 to 0.010. Conclusions These extensions will allow for better personalised risks for BARD1 , RAD51C , RAD51D and PALB2 pathogenic variant carriers and more informed choices on screening, prevention, risk factor modification or other risk-reducing options.

Risk assessment and genetic counseling for hereditary breast and ovarian cancer syndromes—Practice resource of the National Society of Genetic Counselors

AbstractCancer risk assessment and genetic counseling for hereditary breast and ovarian cancer (HBOC) are a communication process to inform and prepare patients for genetic test results and the related medical management. An increasing number of healthcare providers are active in the delivery of cancer risk assessment and testing, which can have enormous benefits for enhanced patient care. However, genetics professionals remain key in the multidisciplinary care of at‐risk patients and their families, given their training in facilitating patients’ understanding of the role of genetics in cancer development, the potential psychological, social, and medical implications associated with cancer risk assessment and genetic testing. A collaborative partnership of non‐genetics and genetics experts is the ideal approach to address the growing number of patients at risk for hereditary breast and ovarian cancer. The goal of this practice resource is to provide allied health professionals an understanding of the key components of risk assessment for HBOC as well as the use of risk models and published guidelines for medical management. We also highlight what patient types are appropriate for genetic testing, what are the most appropriate test(s) to consider, and when to refer individuals to a genetics professional. This practice resource is intended to serve as a resource for allied health professionals in determining their approach to delivering comprehensive care for families and individuals facing HBOC. The cancer risk and prevalence figures in this document are based on cisgender women and men; the risks for transgender or non‐binary individuals have not been studied and therefore remain poorly understood.

Hereditary breast and ovarian cancer (HBOC): review of its molecular characteristics, screening, treatment, and prognosis

AbstractBreast cancer is a common cancer affecting a large number of patients. Notably, 5–10% of all breast cancer patients are genetically predisposed to cancers. Although the most common breast cancer susceptibility genes areBRCA1andBRCA2, which are also associated with the risk of developing ovarian and pancreatic cancer, advances in next-generation sequencing (NGS) analysis technology enabled the discovery of several non-BRCAgenes responsible for breast and ovarian cancers. Studies on hereditary breast and ovarian cancer (HBOC) involve not only determining the predisposition to developing cancer, but also considering the current treatment for breast cancer, prevention of next cancer, risk diagnosis, and adoption of protective measures for relatives. We present a comprehensive review of HBOC, which will be a useful resource in the clinical setting. Many hereditary tumors, including HBOC, are syndromes characterized by the development of different types of cancer in succession. Taking advantage of knowing predisposition of susceptibility to cancer, it is important to continue and update cancer management protocols, which includes the adoption of preventive measures, countermeasures, and treatments, to accurately assess and prevent the impact of cancer on the quality of life of the next generation of patients.

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic provide recommendations for genetic testing and counseling for hereditary cancer syndromes, and risk management recommendations for patients who are diagnosed with syndromes associated with an increased risk of these cancers. The NCCN panel meets at least annually to review comments, examine relevant new data, and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panel’s discussion and most recent recommendations regarding criteria for high-penetrance genes associated with breast and ovarian cancer beyond BRCA1/2, pancreas screening and genes associated with pancreatic cancer, genetic testing for the purpose of systemic therapy decision-making, and testing for people with Ashkenazi Jewish ancestry.

Andrew Lee

Antonis C. Antoniou

Paul D P Pharoah

Peter Devilee

Reiko Yoshida