Personalised Risk Prediction in Hereditary Breast and Ovarian Cancer: A Protocol for a Multi-Centre Randomised Controlled Trial
1
Primary Care Unit, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge CB1 8RN, UK
2
Department of Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK
3
Academic Department of Medical Genetics, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
4
Manchester Centre for Genomic Medicine, St. Marys Hospital, Oxford Road, Manchester M13 9WL, UK
5
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
6
Cambridge Genomics Laboratory, Cambridge University Hospitals Foundation Trust, Hills Road, Cambridge CB2 0QQ, UK
7
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA
8
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge CB1 8RN, UK
9
Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA 94305, USA
10
Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PL, UK
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Academic Editor: Mineko Terao
Cancers 2022, 14(11), 2716; https://doi.org/10.3390/cancers14112716
Received: 1 April 2022
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Revised: 27 May 2022
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Accepted: 28 May 2022
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Published: 31 May 2022
(This article belongs to the Special Issue Advances in Inherited Breast and Ovarian Cancer and Its Imaging)
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.
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Keywords:
personalised risk prediction; breast cancer; epithelial ovarian cancer; CanRisk; polygenic risk scores; genetics
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MDPI and ACS Style
Archer, S.; Fennell, N.; Colvin, E.; Laquindanum, R.; Mills, M.; Dennis, R.; Stutzin Donoso, F.; Gold, R.; Fan, A.; Downes, K.; Ford, J.; Antoniou, A.C.; Kurian, A.W.; Evans, D.G.; Tischkowitz, M. Personalised Risk Prediction in Hereditary Breast and Ovarian Cancer: A Protocol for a Multi-Centre Randomised Controlled Trial. Cancers 2022, 14, 2716. https://doi.org/10.3390/cancers14112716
AMA Style
Archer S, Fennell N, Colvin E, Laquindanum R, Mills M, Dennis R, Stutzin Donoso F, Gold R, Fan A, Downes K, Ford J, Antoniou AC, Kurian AW, Evans DG, Tischkowitz M. Personalised Risk Prediction in Hereditary Breast and Ovarian Cancer: A Protocol for a Multi-Centre Randomised Controlled Trial. Cancers. 2022; 14(11):2716. https://doi.org/10.3390/cancers14112716
Chicago/Turabian StyleArcher, Stephanie, Nichola Fennell, Ellen Colvin, Rozelle Laquindanum, Meredith Mills, Romy Dennis, Francisca Stutzin Donoso, Rochelle Gold, Alice Fan, Kate Downes, James Ford, Antonis C. Antoniou, Allison W. Kurian, D. Gareth Evans, and Marc Tischkowitz. 2022. "Personalised Risk Prediction in Hereditary Breast and Ovarian Cancer: A Protocol for a Multi-Centre Randomised Controlled Trial" Cancers 14, no. 11: 2716. https://doi.org/10.3390/cancers14112716
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