CRediT contribution statement
David P French (https://orcid.org/0000-0002-7663-7804): Conceptualisation (joint lead), Data curation, Formal analysis, Funding acquisition (joint lead), Methodology, Project administration, Supervision, Validation, Visualisation, Writing – original draft (lead).
Lorna McWilliams (https://orcid.org/0000-0002-6414-2732): Data curation, Formal analysis, Investigation, Validation, Writing – original draft.
Katherine Payne (https://orcid.org/0000-0002-3938-4350): Conceptualisation, Funding acquisition, Methodology, Resources, Supervision, Validation, Writing – reviewing and editing.
Victoria G Woof (https://orcid.org/0000-0003-4069-5188): Data curation, Formal analysis, Investigation, Validation, Writing – original draft.
Fiona Harrison (https://orcid.org/0000-0002-9943-9720): Conceptualisation, Funding acquisition, Validation, Writing – reviewing and editing.
Andrew Jerrison (https://orcid.org/0000-0002-7906-241X): Data curation, Formal analysis, Investigation, Methodology, Resources, Software, Validation, Visualisation, Writing – original draft.
Matthew Machin (https://orcid.org/0000-0001-6600-9508): Data curation, Formal analysis, Methodology, Resources, Software, Supervision, Validation, Visualisation, Writing – original draft.
Stuart J Wright (https://orcid.org/0000-0002-4064-7998): Data curation, Formal analysis, Validation, Visualisation, Writing – original draft.
Anthony Howell (https://orcid.org/0000-0002-6233-719X): Conceptualisation, Funding acquisition, Resources, Validation, Writing – reviewing and editing.
Sacha J Howell (https://orcid.org/0000-0001-8141-6515): Resources, Validation, Writing – reviewing and editing.
Louise S Gorman (https://orcid.org/0000-0002-6570-7272): Formal analysis, Investigation, Validation, Writing – reviewing and editing.
Helen Ruane (https://orcid.org/0000-0002-0114-0123): Formal analysis, Investigation, Writing – reviewing and editing.
Fiona Ulph (https://orcid.org/0000-0003-3590-6542): Conceptualisation, Funding acquisition, Methodology, Validation, Writing – reviewing and editing.
Nadeem Qureshi (https://orcid.org/0000-0003-4909-0644): Conceptualisation, Funding acquisition, Methodology, Validation, Writing – reviewing and editing.
Rachel Hawkins (https://orcid.org/0000-0003-1837-4409): Formal analysis, Investigation, Validation, Writing – reviewing and editing.
Susan Astley (https://orcid.org/0000-0002-2989-2765): Conceptualisation, Funding acquisition, Methodology, Resources, Validation, Writing – reviewing and editing.
Anthony J Maxwell (https://orcid.org/0000-0001-8344-4958): Conceptualisation, Funding acquisition, Methodology, Validation, Writing – reviewing and editing.
Gillian Hutchison (https://orcid.org/0000-0002-4511-869X): Project administration, Resources, Writing – reviewing and editing.
Richard Dobrashian (https://orcid.org/0000-0001-8406-5909): Funding acquisition, Project administration, Resources, Writing – reviewing and editing.
Sarah Bowers (https://orcid.org/0000-0002-1818-726X): Project administration, Writing – reviewing and editing.
Paula Stavrinos (https://orcid.org/0009-0006-2285-9301): Project administration, Writing – reviewing and editing.
Sarah Sampson (https://orcid.org/0009-0008-6175-8508): Project administration, Writing – reviewing and editing.
Jake Southworth (https://orcid.org/0000-0002-7099-4368): Project administration.
Emma Thorpe (https://orcid.org/0009-0008-8485-6418): Project administration.
Michelle Harvie (https://orcid.org/0000-0001-9761-3089): Conceptualisation, Funding acquisition, Methodology, Writing – reviewing and editing.
Elaine F Harkness (https://orcid.org/0000-0001-6625-7739): Formal analysis, Validation, Writing – reviewing and editing.
Lynne Fox (https://orcid.org/0000-0003-3891-3190): Project administration.
Adam R Brentnall (https://orcid.org/0000-0001-6327-4357): Formal analysis, Validation, Methodology, Writing – reviewing and editing.
Jack Cuzick (https://orcid.org/0000-0001-7420-7512): Conceptualisation, Funding acquisition, Methodology, Resources, Software, Validation, Writing – reviewing and editing.
Stephen W Duffy (https://orcid.org/0000-0003-4901-7922): Conceptualisation, Funding acquisition, Methodology, Writing – reviewing and editing.
D Gareth Evans (https://orcid.org/0000-0002-8482-5784): Conceptualisation (joint lead), Data curation, Formal analysis, Funding acquisition (joint lead), Methodology, Project administration, Supervision, Resources, Validation, Visualisation, Writing – original draft.
Acknowledgements
We would like to thank many people who have contributed to the current programme grant in addition to those individuals named as authors on this report. First the various NHS staff who were responsible for running the services at the three sites in the present research (East Lancashire NHS Trust, Manchester University NHS Trust and East Cheshire NHS Trust). Jalal Kokan at East Cheshire NHS Trust supported this research from inception. Ladislava Welton (acting breast screening programme manager) supported the set-up of BC-Predict at East Cheshire NHS Trust. Liz Read (breast imaging manager) at East Lancashire supported the research in multiple ways, including attending some PROCAS2 team meetings and supporting recruitment of the final interview study with HCPs. Dr Yit Lim (consultant radiologist at Manchester University NHS Foundation Trust) supported some of the manual density calculations during BC-Predict. At Nightingale FHPC, Mayadar Haydar and Andrea Wilding provided risk consultations to women at higher risk. Manchester University NHS Foundation Trust was the study sponsor. The PROCAS2 administration team notably included Tahiya Zaman, Alice Hendy, Faiza Idries, Hanaa Ghaffar-Manan, Jill Fox, Amy Woodhouse and Manpreet Bharj. In-person data collection (including DNA collection) included Jasmine Egan, Sarah Gibbons and Helen Byers (who was also involved in SNP analysis). Hayley Brooks was responsible at MFT for regulatory approvals. Nasaim Khan was instrumental in linking the research team with the British-Pakistani population in East Lancashire. This work was also facilitated by community outreach workers via St Mary’s Genetic Counselling Service, notably Wahida Pervaiz, Tanis Barnett, Arry Nessa, Yasmine Choudry and Iqbal Bhai. The implementation of BC-Predict relied on the input of Volpara Solutions, especially Chris Tromans and CRA Health. Tjeerd van Staa provided advice on this process. Other staff at The University of Manchester helped with the developmental work and agenda setting meeting, particularly Sarah Hindmarch, Rhiannon Hawkes and Dr Rachel Cholerton. The following people contributed to the health economic model validation: Anna Donten, Rob Hainsworth, Ewan Gray and Gabriel Rogers. Matt Baxter provided communications support. The programme steering group was Professor Per Hall (chair), Professor Katie Robb, Dr Suzette Delaloge and Mr Mark Sibbering. The research would not have been possible without the input of the PPIE group, which was supported by VOCAL. Input into PPIE was also received from the North West League of Jewish Women, Lancashire Women’s Centres and AAWAZ Asian Women’s Group. Finally, we are grateful to the thousands of women in North West England who participated in the present research. We would like to thank many people who have contributed to the current programme grant in addition to those individuals named as authors on this report. Jalal Kokan: funding acquisition; resources. Ladislava Welton: resources. Liz Read: project administration; resources. Yit Lim: investigation. Mayadar Haydar: resources. Andrea Wilding: resources. Tahiya Zaman: project administration. Alice Hendy: project administration. Faiza Idries: project administration. Hanaa Ghaffar-Manan: project administration. Jill Fox: project administration. Amy Woodhouse: project administration. Manpreet Bharj: project administration. Jasmine Egan: investigation. Sarah Gibbons: investigation. Helen Byers: investigation. Hayley Brooks: administration. Nasaim Khan: methodology; investigation. Wahida Pervaiz: investigation. Tanis Barnett: investigation. Arry Nessa: investigation. Yasmine Choudry: investigation. Iqbal Bhai: investigation. Chris Tromans: resources; software. Tjeerd van Staa: funding acquisition; methodology. Sarah Hindmarch: investigation. Rhiannon Hawkes: investigation; Rachel Cholerton: investigation. Anna Donten: investigation; validation. Rob Hainsworth: investigation; validation. Ewan Gray: investigation; validation. Gabriel Rogers: investigation; validation. Matt Baxter: project administration.
The programme steering group included Professor Per Hall (chair), Professor Katie Robb, Dr Suzette Delaloge and Mr Mark Sibbering. The research would not have been possible without the input of the PPIE group, which was supported by VOCAL. Input into PPIE was also received from the North West League of Jewish Women, Lancashire Women’s Centres and AAWAZ Asian Women’s Group. Finally, we are grateful to the thousands of women in North West England who participated in the present research.
Patient data statement
This work uses data provided by patients and collected by the NHS as part of their care and support. Using patient data is vital to improve health and care for everyone. There is huge potential to make better use of information from people’s patient records, to understand more about disease, develop new treatments, monitor safety and plan NHS services. Patient data should be kept safe and secure, to protect everyone’s privacy, and it’s important that there are safeguards to make sure that they are stored and used responsibly. Everyone should be able to find out about how patient data are used. #datasaveslives You can find out more about the background to this citation here: https://understandingpatientdata.org.uk/data-citation
Data-sharing statement
All data requests should be submitted to the corresponding author for consideration. All available quantitative data that are in anonymised form can be obtained from the corresponding author on reasonable request. Requests to access some qualitative data should also be made to the corresponding authors. Please note that requests to access some qualitative data may be declined to protect the confidentiality of participants.
Ethics statement
NHS ethical approval for the PROCAS2 study was granted by Harrow Research Ethics Committee on 9 July 2018 (ref. 18/LO/0649)/ IRAS project ID 239199.
Information governance statement
The University of Manchester is committed to handling all personal information in line with the UK Data Protection Act (2018) and the General Data Protection Regulation (EU GDPR) 2016/679. Under the Data Protection legislation, the University of Manchester is the Data Processor; Manchester University NHS Foundation Trust is the Data Controller and we process personal data in accordance with their instructions. You can find out more about how we handle personal data, including how to exercise your individual rights and the contact details for Manchester University NHS Foundation Trust’s Data Protection Officer here: https://mft.nhs.uk/app/uploads/2021/12/Privacy-Notice-Apr-21-v0.7-Booklet.pdf
Disclosure of interests
Full disclosure of interests: Completed ICMJE forms for all authors, including all related interests, are available in the toolkit on the NIHR Journals Library report publication page at https://doi.org/10.3310/HGDW6751
Primary conflicts of interest: David P French has received funding from NHIR PROCAS2 Programme Grant (ref.: RP-PG-1214-20016) for the present research. He has received further funding for the present research through two project grants from Genesis Breast Cancer Prevention (GA15-003) and Breast Cancer Now (2018RP005) and the Manchester Biomedical Research Centre (IS-BRC-1215-20007) infrastructure grant. He has received further funding for research in the area of this grant from Cancer Research UK, European Commission Horizon 2020, Prevent Breast Cancer and Manchester Cancer Research Centre and infrastructure support from the Manchester NIHR Applied Research Collaboration. David P French was a panel member for the Research Excellence Framework (REF) 2021, sub-panel 2: Public Health, Health Services and Primary Care.
Lorna McWilliams received funding from NIHR PROCAS2 Programme Grant (ref.: RP-PG-1214-20016); Salary paid in part from this grant (1 September 2020 to 30 June 2022), NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007); supported administratively by this centre award, UMRI Interdisciplinary Research Pump-prime Project Award (award number tbc); Co-investigator; awarded, to start September 2022, Cancer Research UK Early Detection Committee Project Award (A27836); Co-Investigator, Breast Cancer Now Project Award (2018RP005); salary paid in part from this grant (October 2018 to 28 February 2022); closed grant, CRUK International Alliance for Early Detection on Cancer (ACED; A29320); Grant holder; closed grant.
Katherine Payne received funding from NIHR PROCAS2 Programme Grant (ref.: RP-PG-1214-20016) and Genesis Breast Cancer Prevention (GA15-003), Breast Cancer Now (2018RP005).
Victoria Woof Medical Research Council PhD Studentship, ref.: MR/N013751/1.
Fiona Harrison received payment for her participation in this research (expenses/travel).
Stuart J Wright received funding from Cancer Research UK (Co-App) A Case Control Study of women aged 30–39 to augment breast cancer risk prediction and assess acceptability and preference of a systematic risk prediction approach through primary care.
Anthony Howell received funding from Genesis Breast Cancer Prevention (GA15-003).
Sacha Howell received funding from NHIR PROCAS2 Programme Grant (ref.: RP-PG-1214-20016), Cancer Research UK Project grant (CI), Breast Cancer Now Project grant (Co-App), Breast Cancer Now BRCA-P Trial (CI) and NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007) and has received payment from Eli-Lilly for participation on an Advisory Board and is Deputy Chair on the Breast Cancer Now grant review committee.
Jack Cuzick receives royalties for commercial use of the Tyrer–Cuzick (IBIS) breast cancer risk evaluator.
Louise S Gorman received funding from NIHR PROCAS2 Programme Grant (ref.: RP-PG-1214-20016).
Fiona Ulph received funding from NIHR PROCAS2 Programme Grant (ref.: RP-PG-1214-20016) AND Breast Cancer Now.
Rachel Hawkins received funding from NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007).
Susan Astley received funding NIHR PROCAS2 Programme Grant (ref.: RP-PG-1214-20016), Cancer Research UK Project grant (Co-I), CIHR grant (CI).
Anthony J Maxwell received funding from NIHR PROCAS2 Programme Grant (ref.: RP-PG-1214-20016), NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007), Genesis Breast Cancer Prevention (GA15-003) and Breast Cancer Now (2018RP005).
Emma Thorpe received funding from NIHR PROCAS2 Programme Grant (ref.: RP-PG-1214-20016) and NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007).
Michelle Harvie received funding from NIHR PROCAS2 Programme Grant (ref.: RP-PG-1214-20016), NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007), Genesis Breast Cancer Prevention (GA15-003), Breast Cancer Now (2018RP005).
Elaine F Harkness received funding from NIHR PROCAS2 Programme Grant (ref.: RP-PG-1214-20016) and NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007).
Richard Dobrashian received funding from NIHR PROCAS2 Programme Grant (ref.: RP-PG-1214-20016).
Adam R Brentnall received funding from Cancer Research UK, Breast Cancer Now, Barts Charity, NIHR and royalties for commercial use of the Tyrer–Cuzick (IBIS) breast cancer risk evaluator.
D Gareth Evans has received consultancies from Astrazeneca related to PARPi treatments that are not relevant to this research.
Copyright and credit statement
Every effort has been made to obtain the necessary permissions for reproduction, to credit original sources appropriately and to respect copyright requirements. However, despite our diligence, we acknowledge the possibility of unintentional omissions or errors and we welcome notifications of any concerns regarding copyright or permissions.
Publications
French DP, Astley S, Brentnall AR, Cuzick J, Dobrashian R, Duffy SW, et al. What are the benefits and harms of risk stratified screening as part of the NHS Breast Screening Programme? Study protocol for a multi-site non-randomised comparison of BC-Predict versus usual screening (NCT04359420). BMC Cancer 2020;20:570. https://doi.org/10.1186/s12885-020-07054-2
Woof VG, Ruane H, Ulph F, French DP, Qureshi N, Khan N, et al. Engagement barriers and service inequities in the NHS breast screening programme: views from British-Pakistani women. J Med Screen 2020;27:130–37. https://doi.org/10.1177/0969141319887405
Woof VG, Ruane H, Ulph F, French DP, Qureshi N, Khan N, et al. The introduction of risk stratified screening into the NHS breast screening programme: views from British-Pakistani women. BMC Cancer 2020;20:1–9. https://doi.org/10.1186/s12885-020-06959-2
French DP, Woof VG, Ruane H, Evans DG, Ulph F, Donnelly LS. The feasibility of implementing risk stratification into a national breast cancer screening programme: perspectives of healthcare personnel responsible for delivery. BMC Women Health 2022;22:142. https://doi.org/10.1186/s12905-022-01730-0
McWilliams L, Evans DG, Payne K, Harrison F, Howell A, Howell SJ, et al., on behalf of the Breast Screening Risk-Stratification Agenda Setting Group. Implementing risk stratified breast screening in England: an agenda setting meeting. Cancers 2022;14:4636. https://doi.org/10.3390/cancers14194636
Gorman LS, Ruane H, Woof V, Southworth J, Ulph F, DG Evans, et al. The co-development of personalized 10-year breast cancer risk communications: a ‘think aloud’ study. BMC Cancer 2022;22:1264. https://doi.org/10.1186/s12885-022-10347-3
Evans DG, McWilliams L, Astley S, Brentnall AR, Cuzick J, Dobrashian R, et al. Quantifying the effects of risk stratified breast cancer screening when delivered in real time as routine practice versus usual screening: the BC-Predict non-randomised controlled study Br J Cancer 2023;128:2063–71. https://doi.org/10.1038/s41416-023-02250-w
French DP, McWilliams L, Bowers S, Woof V, Harrison F, Ruane H, et al. Psychological impact of risk stratified screening as part of the NHS Breast Screening Programme: multi-site non-randomised comparison of BC-Predict versus usual screening (NCT04359420). Br J Cancer 2023;128:1548–58. https://doi.org/10.1038/s41416-023-02156-7
Hawkins R, McWilliams L, Ulph F, Evans DG, French DP. Healthcare professionals’ views following implementation of risk stratification into a national breast cancer screening programme. BMC Cancer 2023;22:1058. https://doi.org/10.1186/s12885-022-10134-0
Khattak H, Woof V, French DP, Donnelly L, Ruane H, Ulph F, et al. The role of knowledge, primary care, and community engagement to improve breast screening access for Pakistani women in the UK: a secondary analysis of a qualitative study. J Health Serv Res Policy 2023;28;149–56. https://doi.org/10.1177/13558196231155824
McWilliams L, Ruane H, Ulph F, Woof VG, Harrison F, Evans DG, et al. What do women think about having received their breast cancer risk as part of a risk stratified NHS Breast Screening Programme? A qualitative study. Br J Cancer 2023;129:356–65. https://doi.org/10.1038/s41416-023-02268-0
Woof VG, McWilliams L, Howell A, Evans DG, French DP. How do women at increased risk of breast cancer make sense of their risk? An interpretative phenomenological analysis. Br J Health Psychol 2023;28;1169–84. https://doi.org/10.1111/bjhp.12678
Wright SJ, Eden M, Ruane H, Byers H, Evans DG, Harvie M, et al. Estimating the cost of 3 risk prediction strategies for potential use in the United Kingdom national Breast Screening Programme. MDM Policy Pract 2023;8:1171363. https://doi.org/10.1177/23814683231171363
Wright SJ, Gray E, Rogers G, Donten A, Payne K. A structured process for the validation of a decision-analytic model: application to a cost-effectiveness model for risk-stratified national breast screening. Appl Health Econ Health Policy 2024;22:527–42. https://doi.org/10.1007/s40258-024-00887-z
Wright SJ, Rogers G, Gray E, Donten A, McWilliams L, French DP, et al. Evaluation of a risk-stratified national breast screening programme in the United Kingdom: an updated cost-effectiveness analysis. medRxiv 2024. URL: www.medrxiv.org/content/10.1101/2024.04.16.24305897v1 (accessed 24 October 2024).
Disclaimers
This article presents independent research funded by the National Institute for Health and Care Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, CCF, PGfAR or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, the PGfAR programme or the Department of Health and Social Care.