Assessing the impact of personalised risk estimates on the uptake and timing of risk management options in women who have inherited a change in genes associated with an increased risk of breast and ovarian cancer
| ISRCTN | ISRCTN15331714 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15331714 |
| IRAS number | 291629 |
| Secondary identifying numbers | CPMS 48658, CRUK C22770/A31523, IRAS 291629 |
- Submission date
- 18/03/2022
- Registration date
- 21/06/2022
- Last edited
- 02/05/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
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 (BRCA1, BRCA2, PALB2 only). At present, the risk estimates given by most health practitioners to women 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 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.
Who can participate?
Women who are referred to the Genetics department to discuss “predictive” genetic testing are eligible for this study. Predictive genetic testing is when a relative has been found to have a gene fault, and a family member wishes to see if they also carry the same gene change. To participate, women must be over the age of 18 and able to give informed consent. A woman is not able to take part in this study if she has had a previous diagnosis of breast or ovarian cancer.
What does the study involve?
Genetic testing will be performed in the usual way. If the test shows that the participant has inherited the gene change, they will be randomly allocated to have a standard risk estimate or the “personalised” risk estimate, using a risk prediction tool called CanRisk. If they are allocated to the “personalised” arm, we will do some additional genetic testing on the blood sample the patient gave to look at the hundreds of small genetic alterations and provide them with a combined risk estimate, called a Polygenic Risk Score (PRS). Both groups will be asked to complete some questionnaires. This would include one questionnaire before their clinical genetics appointment, followed by three more “follow-up” questionnaires after they receive their genetics result. Participants may be invited to give an interview with one of the research team. In this research study we will use information from the participant, their medical records, their GP and from NHS Digital. We will only use information that we need for the research study. Everyone involved in this study will keep participant data safe and secure following all privacy rules.
What are the possible benefits and risks of participating?
The participant will receive a different risk estimate depending on which group of the study they are randomised to. This could involve additional analysis than the standard genetic test (the analysis will be done on the same blood sample they gave for genetic testing). Our aim is to study how these differences affect the participant’s subsequent decisions regarding their medical management. There is no direct benefit to the participant. However, by taking part in our research study participants will potentially be helping future generations of women with these gene changes. We will publish our findings on our website and/or in a newsletter.
We will use the sample blood sample as the one given for the clinical genetic test. No additional blood test will be required. There are no medical risks in taking part.
Where is the study run from?
Cambridge University Hospitals NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
June 2021 to December 2026
Who is funding the study?
Cancer Research UK
Who is the main contact?
Dr Marc Tischkowitz, mdt33@cam.ac.uk
Contact information
Scientific
Dept. of Medical Genetics
Addenbrookes Treatment Centre Level 6
Addenbrookes Hospital
Cambridge
CB2 0QQ
United Kingdom
 ORCID ID |
0000-0002-7880-0628 |
|---|---|
| Phone | +44 1223 216446 |
| mdt33@medschl.cam.ac.uk |
Scientific
Dept. of Medical Genetics
Addenbrookes Treatment Centre Level 6
Addenbrookes Hospital
Cambridge
CB2 0QQ
United Kingdom
| ORCID ID |
0000-0002-5711-6341 |
|---|---|
| Phone | +44 1223 216446 |
| nf381@medschl.cam.ac.uk |
Study information
| Study design | Interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | 41380 PIS v2.0 18Nov2021.pdf |
| Scientific title | Stratifying risk for early detection in hereditary breast and ovarian cancer |
| Study acronym | Precision-HBOC |
| Study objectives | The timing and uptake of risk management options will be different between women who receive the personalised risk estimates compared to women who receive the broad-range risk estimates, as per current clinical practice. |
| Ethics approval(s) | Approved 21/05/2021, East of England - Cambridgeshire and Hertfordshire Research Ethics Committee (Temple Quay House, 2 The Square, Bristol Research Ethics Committee Centre, BS1 6PN, UK; +44 2071048278; cambsandherts.rec@hra.nhs.uk), ref: 21/EE/0062 |
| Health condition(s) or problem(s) studied | Hereditary breast and ovarian cancer |
| Intervention | Women who agree to take part in the study will be asked to complete a short questionnaire which will include basic demographics along with details regarding relevant risk factors (family history of cancer, height, body mass index, parity, age at first birth, age at menarche, age at menopause, use of oral contraception, use of hormone replacement therapy, alcohol intake). They will have a standard predictive test performed in the local clinical laboratory in the study and, if the result shows that they have inherited the mutation, a DNA aliquot (from the original blood sample taken for genetic testing) will be sent to Cambridge for the 313-SNP PRS. The PRS result, together with the other factors collected in the questionnaire, will be inputted into the CanRisk risk prediction tool to generate personalised risks. |
| Intervention type | Other |
| Primary outcome measure | The type and the timing of risk management options (surveillance, chemoprevention, surgery) taken up over the course of the study (i.e. 12 months) measured via 4 questionnaires (baseline, then 1, 3 and 12 months post-results) |
| Secondary outcome measures | 1. The type of risk management options planned to be taken up in the future (i.e. beyond the end of the study). measured via questionnaires at 1, 3 and 12 months post-results). 2. Informed decision-making about risk management options (measured by combining objective knowledge, attitude and behaviour) measured via questionnaires at 1, 3 and 12 months post-results). 3. Women’s understanding of the test result measured via questionnaires at 1, 3 and 12 months post-results). 4. Psycho-social impact (including cancer worry, anxiety and quality of life), measured via 4 questionnaires (baseline, then at 1, 3 and 12 months post-results). 5. Information on women’s use of health services will also be captured in order to perform a cost-utility analysis measured via 4 questionnaires (baseline, then at 1, 3 and 12 months post-results). 6. Exploring the acceptability and implementation of personalised risk calculations in clinical genetics services measured by semi-structured interviews with patients and staff at 12 months. |
| Overall study start date | 01/06/2021 |
| Completion date | 31/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 600; UK Sample Size: 400 |
| Key inclusion criteria | 1. Female 2. Age >18 years 3. Undergoing predictive testing for a PV in BRCA1, BRCA2, PALB2, ATM or CHEK2 4. Able to give informed consent |
| Key exclusion criteria | Previous history of breast cancer or ovarian cancer |
| Date of first enrolment | 01/05/2022 |
| Date of final enrolment | 31/12/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
- United States of America
Study participating centres
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Oxford Road
Manchester
M13 9WL
United Kingdom
Palo Alto CA
94305
United States of America
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
Oxford Road
Manchester
M13 9WL
United Kingdom
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Westminster Bridge Road
London
SE1 7EH
United Kingdom
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Queens Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom
Beckett Street
Leeds
LS9 7TF
United Kingdom
Crown Street
Liverpool
L8 7SS
United Kingdom
London
SW17 0QT
United Kingdom
Metchley Park Road
Birmingham
B15 2TG
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
London
WC1N 3JH
United Kingdom
Sponsor information
Hospital/treatment centre
Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom
| Phone | +44 1223348494 |
|---|---|
| research@addenbrookes.net | |
| Website | http://www.cuh.org.uk/ |
"ROR" |
https://ror.org/04v54gj93 |
University/education
Department of Medical Genetics
University of Cambridge - School of Clinical Medicine
Box 238
Level 6 Addenbrooke's Treatment Centre
Cambridge Biomedical Campus
Cambridge
CB2 0QQ
England
United Kingdom
| Phone | +44 1223 216 446 |
|---|---|
| researchgovernance@medschl.cam.ac.uk | |
| Website | http://www.cam.ac.uk/ |
|
"ROR" |
https://ror.org/013meh722 |
Funders
Funder type
Charity
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/05/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to ethical approval not being granted to share data |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 2.0 | 18/11/2021 | 07/04/2022 | No | Yes |
| Protocol article | 31/05/2022 | 21/06/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
02/05/2025: The contact confirmed the record is up to date.
29/04/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 30/04/2024 to 31/12/2025.
2. The overall study end date was changed from 31/05/2024 to 31/12/2026.
3. The intention to publish date was changed from 30/05/2025 to 30/05/2027.
4. Cambridge University Hospital, University Hospital Southampton, Manchester Foundation Trust, University Hospitals Leicester, Guy's and St Thomas' NHS Foundation Trust, Oxford University Hospital, Nottingham University Hospitals NHS Trust, Leeds Teaching Hospitals NHS Trust, Liverpool Womens NHS Foundation Trust, St George's University Hospitals NHS Foundation Trust, Birmingham Women's Hospital, Royal Devon and Exeter Hospital and Great Ormond Street Hospital were added to the study participating centres.
18/03/2022: Trial's existence confirmed by the National Institute for Health Research (NIHR) (UK).
