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)

Abstract

Background In principle, risk-stratification as a routine part of the NHS Breast Screening Programme (NHSBSP) should produce a better balance of benefits and harms. The main benefit is the offer of NICE-approved more frequent screening and/ or chemoprevention for women who are at increased risk, but are unaware of this. We have developed BC-Predict, to be offered to women when invited to NHSBSP which collects information on risk factors (self-reported information on family history and hormone-related factors via questionnaire; mammographic density; and in a sub-sample, Single Nucleotide Polymorphisms). BC-Predict produces risk feedback letters, inviting women at high risk (≥8% 10-year) or moderate risk (≥5 to < 8% 10-year) to have discussion of prevention and early detection options at Family History, Risk and Prevention Clinics. Despite the promise of systems such as BC-Predict, there are still too many uncertainties for a fully-powered definitive trial to be appropriate or ethical. The present research aims to identify these key uncertainties regarding the feasibility of integrating BC-Predict into the NHSBSP. Key objectives of the present research are to quantify important potential benefits and harms, and identify key drivers of the relative cost-effectiveness of embedding BC-Predict into NHSBSP. Methods A non-randomised fully counterbalanced study design will be used, to include approximately equal numbers of women offered NHSBSP (n = 18,700) and BC-Predict (n = 18,700) from selected screening sites (n = 7). In the initial 8-month time period, women eligible for NHSBSP will be offered BC-Predict in four screening sites. Three screening sites will offer women usual NHSBSP. In the following 8-months the study sites offering usual NHSBSP switch to BC-Predict and vice versa. Key potential benefits including uptake of risk consultations, chemoprevention and additional screening will be obtained for both groups. Key potential harms such as increased anxiety will be obtained via self-report questionnaires, with embedded qualitative process analysis. A decision-analytic model-based cost-effectiveness analysis will identify the key uncertainties underpinning the relative cost-effectiveness of embedding BC-Predict into NHSBSP. Discussion We will assess the feasibility of integrating BC-Predict into the NHSBSP, and identify the main uncertainties for a definitive evaluation of the clinical and cost-effectiveness of BC-Predict. Trial registration Retrospectively registered with clinicaltrials.gov (NCT04359420).

Risk stratified breast cancer screening: UK healthcare policy decision-making stakeholders’ views on a low-risk breast screening pathway

“…Members of the research team (DGE, AH) have been involved in policy-level work regarding risk-stratified screening which may have influenced respondents' interest in participating in the study and expressed opinions, although these team members were not involved in study data collection or analysis. Further, the team are involved in research in this area [41]. It could be that individuals who participated have a more favourable opinion of risk stratified breast screening, although the high rate of uptake of interviews by professionals with multiple demands on time suggests that this was not a major threat to the validity of these findings.…”

Long-Term Evaluation of Women Referred to a Breast Cancer Family History Clinic (Manchester UK 1987–2020)

“…We are currently testing the feasibility of introducing identification and referral of higher risk women as part of routine screening, i.e., research with a focus on implementation as part of routine care in a NHSBSP could bring about a “step change” if implemented [ 6 ]. There is already some evidence that communicating breast cancer risk estimates as part of routine screening does not produce the harms that have been anticipated [ 99 ]. For instance, communicating risk estimates in this setting did not produce adverse emotional effects or effects on screening uptake [ 100 ].…”

“…If made widely available this could lead to patient-initiated referral for initial screening and SNP estimation to define definitive management [ 105 ]. Other measures may be to establish one-off breast density assessment for all women at a certain age (e.g., 40 years, as suggested above) to estimate BC risk and introduce further screening and preventive measures for those found to be at high risk [ 99 , 106 ].…”

Feasibility and acceptability of personalised breast cancer screening (DECIDO study): protocol of a single-arm proof-of-concept trial

“…On the basis of the PROCAS project, and considering the National Institute for Health and Care Excellence clinical guidelines for women with familial breast cancer, French et al 17 developed an automated system (BC-Predict) for offering an assessment of breast cancer risk to women when they receive their National Health Service Breast Screening Programme (NHSBSP) invitation, and generating feedback letters to communicate this risk to women and health professionals. The recently published protocol describes that the study aims at identifying and resolving key uncertainties regarding the feasibility of integrating BC-Predict into the NHSBSP.…”

“…The recently published protocol describes that the study aims at identifying and resolving key uncertainties regarding the feasibility of integrating BC-Predict into the NHSBSP. 17 In addition to including an explicit quantitative and qualitative analysis of the effects of implementing the BC-Predict system in the NHSBSP, the research will assess the feasibility of a definitive study to evaluate whether the intervention translates into measurable effects on breast cancer incidence and stage, and is a cost-effective use of the National Health Service resources.…”