부산대학교 도서관

Simple Summary: Women with disease-causing gene changes (faults/mutations) in BRCA1, BRCA2, PALB2, CHEK2 and ATM are at an increased risk of developing certain types of cancer—specifically breast (all genes) and epithelial ovarian cancer (only BRCA1, BRCA2, PALB2). At present, the risk estimates given to women by most healthcare professionals are broad (e.g., 35–85% lifetime risk of breast cancer for BRCA1 and BRCA2) and are not personalised. This can make it difficult for women to make informed decisions regarding the risk-management options available to them. By combining information about genetic, lifestyle and hormonal risk factors, we can produce a narrower, more personalised risk estimate (e.g., 44% lifetime risk of breast cancer). In this study, we aim to test whether offering personalised risk estimates to women undergoing predictive testing in genetics centres in the UK and USA better supports women's mental health and choices about their clinical care, relative to standard care. In addition, we will explore the experiences of both staff and women taking part in the study, to understand whether personalised risk estimates are acceptable, feasible and cost-effective for use in clinical care. Women who test positive for an inherited pathogenic/likely pathogenic gene variant in BRCA1, BRCA2, PALB2, CHEK2 and ATM are at an increased risk of developing certain types of cancer—specifically breast (all) and epithelial ovarian cancer (only BRCA1, BRCA2, PALB2). Women receive broad cancer risk figures that are not personalised (e.g., 44–63% lifetime risk of breast cancer for those with PALB2). Broad, non-personalised risk estimates may be problematic for women when they are considering how to manage their risk. Multifactorial-risk-prediction tools have the potential to deliver personalised risk estimates. These may be useful in the patient's decision-making process and impact uptake of risk-management options. This randomised control trial (registration number to follow), based in genetic centres in the UK and US, will randomise participants on a 1:1 basis to either receive conventional cancer risk estimates, as per routine clinical practice, or to receive a personalised risk estimate. This personalised risk estimate will be calculated using the CanRisk risk prediction tool, which combines the patient's genetic result, family history and polygenic risk score (PRS), along with hormonal and lifestyle factors. Women's decision-making around risk management will be monitored using questionnaires, completed at baseline (pre-appointment) and follow-up (one, three and twelve months after receiving their risk assessment). The primary outcome for this study is the type and timing of risk management options (surveillance, chemoprevention, surgery) taken up over the course of the study (i.e., 12 months). The type of risk-management options planned to be taken up in the future (i.e., beyond the end of the study) and the potential impact of personalised risk estimates on women's psychosocial health will be collected as secondary-outcome measures. This study will also assess the acceptability, feasibility and cost-effectiveness of using personalised risk estimates in clinical care. [ABSTRACT FROM AUTHOR]