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 (NCT04359420)

Gareth Evans, D.; McWilliams, Lorna; Astley, Susan; Brentnall, Adam R.; Cuzick, Jack; Dobrashian, Richard; Duffy, Stephen W.; Gorman, Louise S.; Harkness, Elaine F.; Harrison, Fiona; Harvie, Michelle; Jerrison, Andrew; Machin, Matthew; Maxwell, Anthony J.; Howell, Sacha J.; Wright, Stuart J.; Payne, Katherine; Qureshi, Nadeem; Ruane, Helen; Southworth, Jake; Fox, Lynne; Bowers, Sarah; Hutchinson, Gillian; Thorpe, Emma; Ulph, Fiona; Woof, Victoria; Howell, Anthony; French, David P.

Abstract

Background
Risk stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) could provide a better balance of benefits and harms. We developed BC-Predict, to offer women when invited to the NHSBSP, which collects standard risk factor information; mammographic density; and in a sub-sample, a Polygenic Risk Score (PRS).

Methods
Risk prediction was estimated primarily from self-reported questionnaires and mammographic density using the Tyrer–Cuzick risk model. Women eligible for NHSBSP were recruited. BC-Predict produced risk feedback letters, inviting women at high risk (≥8% 10-year) or moderate risk (≥5–<8% 10-year) to have appointments to discuss prevention and additional screening.

Results
Overall uptake of BC-Predict in screening attendees was 16.9% with 2472 consenting to the study; 76.8% of those received risk feedback within the 8-week timeframe. Recruitment was 63.2% with an onsite recruiter and paper questionnaire compared to <10% with BC-Predict only (P < 0.0001). Risk appointment attendance was highest for those at high risk (40.6%); 77.5% of those opted for preventive medication.

Discussion
We have shown that a real-time offer of breast cancer risk information (including both mammographic density and PRS) is feasible and can be delivered in reasonable time, although uptake requires personal contact. Preventive medication uptake in women newly identified at high risk is high and could improve the cost-effectiveness of risk stratification.

Trial registration
Retrospectively registered with clinicaltrials.gov (NCT04359420).

• Journal Article Type: Article
• Acceptance Date: Mar 20, 2023
• Online Publication Date: Apr 1, 2023
• Publication Date: Jun 15, 2023
• Deposit Date: Nov 16, 2023
• Publicly Available Date: Nov 16, 2023
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Cancer Research UK
• Peer Reviewed: Peer Reviewed
• Volume: 128
• Pages: 2063-2071
• DOI: https://doi.org/10.1038/s41416-023-02250-w
• Keywords: Cancer Research; Oncology
• Public URL: https://nottingham-repository.worktribe.com/output/19296588
• Publisher URL: https://www.nature.com/articles/s41416-023-02250-w
• Additional Information: Received: 26 September 2022; Revised: 28 February 2023; Accepted: 20 March 2023; First Online: 1 April 2023; : JC and ARB report receiving royalty payments through Cancer Research UK for commercial use of the Tyrer-Cuzick algorithm. All other authors report no competing interests.; : NHS ethical approval for the study described in the manuscript was granted by Harrow Research Ethics Committee (ref 18/LO/0649)/ IRAS project ID 239199. All participants in BC-Predict have completed written consent (usually online). All data participants in the comparison (usual NHSBSP) condition will be elicited in aggregate form, so individual consent will not be obtained. All women consented to join BC-Predict as there are no identifiable details.; Free to read: This content has been made available to all.