What Are the Benefits and Harms of Risk Stratified Screening in the NHS Breast Screening Programme: Study Protocol

Study Overview
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Brief Summary
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This study aims to identify key benefits and harms of integrating risk stratification (the BC-Predict intervention) into the NHS Breast Screening Programme. A non-randomised fully counterbalanced study design will be used, whereby women from screening sites will be offered usual NHS Breast Screening Programme or BC-Predict for an eight month period, followed by a cross-over point where women at each site will be offered the other invention during an eight month period.

Detailed Description
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In principle, risk-stratification as a routine part of the NHS breast screening programme (NHS-BSP) should produce a better balance of benefits and harms. The main benefit is the offer of NICE (National Institute of Health and Care Excellence) approved more frequent screening and/ or chemoprevention to be realised for women who are at increased risk, but are unaware of this. The invesigators have developed BC-Predict, which is offered to women when invited to NHS-BSP and collects information on risk factors (self-reported information on family history and hormone-related factors, mammographic density and in a sub-sample, Single Nucleotide Polymorphisms). BC-Predict then produces risk feedback letters, and invites women at moderate or high risk to have discussion of prevention and early detection options at Family History, Risk and Prevention Clinics. Key objectives of the present research are to quantify important potential benefits and harms, and to identify the key drivers of the relative cost-effectiveness of embedding BC-Predict into NHS-BSP. A non-randomised fully counterbalanced study design will be used, to include equal numbers of participants from five screening sites who will be offered NHS-BSP and BC-Predict. Specifically, in the initial 8-month time period, women eligible for NHS-BSP in three screening sites will be offered BC-Predict, whilst women in two screening sites are offered usual NHS-BSP. In the following 8-month time period the study sites switch their offers. In total 16000 women will be invited to BC-Predict, and compared with 16000 women offered standard NHS-BSP. Key potential benefits including uptake of BC-Predict, risk consultations, chemoprevention and additional screening will be obtained from NHS-BSP and Family History, Risk and Prevention Clinic records for both groups. Key potential harms such as increased anxiety will be obtained via self-report questionnaires. Health economic analyses will identify the key uncertainties underpinning the relative cost-effectiveness of embedding BC-Predict into NHS-BSP.

Official Title
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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

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: BC-Predict
* Other: NHS Breast Screening Programme


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: born biologically female, invited for either (a) first breast screening appointment (any age) or: (b) aged 57-63 years (only at East Cheshire and East Lancashire breast screening programmes), able to provide informed consent and complete a risk assessment questionnaire. Exclusion Criteria: previously has had breast cancer, has had bilateral mastectomy, or has previously participated in the related PROCAS (Predicting Risk Of Cancer At Screening) study
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: A non-randomised fully counterbalanced study design will be used, to include equal numbers of participants from all sites who will be offered NHS-BSP and BC-Predict. Specifically, in the initial 8-month time period, women eligible for breast screening in three screening sites will be offered BC-Predict, whilst women in two screening sites are offered usual NHS-BSP. In the following 8-month time period the study sites switch to offer the other intervention (NHS-BSP rather than BC-Predict; and vice versa). This will allow estimates of effect to be obtained from both within-sample and between-sample analyses.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BC-Predict<br>Women will be sent an invitation letter one to two days after their breast screening invitation letter, directing prospective participants to the online risk assessment platform. Once participants have consented to the study online, they will be directed to the BC-Predict risk assessment questionnaire. Assessment of the online questionnaire during the pilot phase estimated that most women would be able to complete this within 30 minutes. Women who complete the questionnaire will receive 10-year breast cancer risk estimates once they have screened negative for breast cancer, based on the Tyrer-Cuzick model, incorporating mammographic density, and for some women, SNPs (single nucleotide polymorphisms). Women who are identified as being at high (>8%) or moderate (5% and <8%) 10-year risk will be offered a consultation to discuss prevention options including prescription of chemoprevention drugs and/ or more frequent mammography as part of the NHS Breast Screening Programme. | Other: BC-Predict<br>* BC-Predict is an automated system for offering an assessment of breast cancer risk to women when they receive their NHS Breast Screening Programme invitation, and generating letters to feedback this risk to women and relevant healthcare professionals. Women at higher risk are offered chemoprevention drugs and additional mammography<br>* Other names: risk stratified screening;|
| Active Comparator: NHS-Breast Screening Programme<br>Usual care in the NHS Breast Screening Programme, which involves mammography every 3 years for the majority of women | Other: NHS Breast Screening Programme<br>* usual care from NHS Breast Screening Programme, consisting of mammography every three years for most women.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prescription of chemoprevention. | Frequency of women taking up initial prescription of chemoprevention drugs (anastrozole/tamoxifen/raloxifene) from Family History, Risk and Prevention Clinic Data will be collected on each of the following aspects of this: (a) participant agrees/disagrees in clinic to take chemoprevention, (b) chemoprevention not appropriate, (c) chemoprevention appropriate but prescription not filled, (d) chemoprevention appropriate and prescription filled. | 6 months after screening appointment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Screening attendance at first offered screening episode | Attendance at NHS Breast Screening Programme appointment | attendance within 6 weeks of first specific appointment offered | 
| Screening attendance within 180 days | Attendance at NHS Breast Screening Programme appointment | within 180 days first appointment offered | 
| number of recalls | number of recalls from NHS Breast Screening programme: (a) technical recalls, (b) for assessment, (c) routine recalls | within 6 months of first appointment offered | 
| Number of breast cancer diagnoses | Number of breast cancers diagnosed | within 6 months of first appointment offered | 
| Uptake of consultation at Family History, Risk and Prevention clinics | Family History, Risk and Prevention clinic attendance, to discuss possibly measures to reduce breast cancer risk | within 6 months of first appointment offered | 
| Enrolment for more frequent screening | Uptake of more frequent screening (e.g. yearly) from NHS Breast Screening programme | within 6 months of first appointment offered | 
| State anxiety | Measured using STAI (Spielberger State Anxiety Inventory) short form. Range 6 to 24. Higher scores indicate higher anxiety. | at 6 months of first appointment offered, controlling for baseline values | 
| Cancer worry | Measured using Lerman Cancer Worry Scale. Range 6 to 24. Higher scores indicate higher cancer worry. | at 6 months of first appointment offered, controlling for baseline values | 
| Informed choices to attend screening or not | Informed choices regarding screening will be estimated from attitudes to screening at baseline, knowledge and screening attendance, using a standard approach reported by Marteau, Dormandy & Michie | at 6 months of first appointment offered, controlling for baseline values | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, Screening, risk stratification, high risk, psychological impact, early detection, mammographic density, chemoprevention, Tyrer-Cuzick, anxiety