Breast Screening - Risk Adaptive Imaging for Density

Study Overview
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Brief Summary
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BRAID is a randomised, multi-centre study assessing the impact of supplementary imaging in the detection of breast cancer in women participating in the UK national breast screening programme who have dense breast tissue.

Detailed Description
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Breast density is a measure of the amount of fibroglandular tissue and is a risk factor for breast cancer. Women with extremely dense breasts are at 4-fold increased breast cancer risk compared to women with 'fatty' breasts. High breast density reduces the sensitivity of mammography increasing the probability of the test missing a cancer. Women with dense breasts have their cancers found when the cancer is larger as they present with interval cancers or their cancers are not detected until the next screening round at a later stage. The UK national breast screening programme (NHS BSP) offers all women aged 50-70 screening with 3-yearly mammograms. It aims to reduce breast cancer mortality by 20% by detecting small cancers thereby reducing the number of late stage diagnoses. However only 53% of the cancers being detected are small (<15mm). This is partly due to masking of cancers by dense breast tissue. This trial addresses how best to screen women with dense breasts for breast cancer. BRAID will randomise women whose recent screening mammogram shows that they have dense breasts to either standard of care (no supplementary imaging) or supplementary imaging with abbreviated MRI (ABB-MRI), automated whole breast ultrasound (ABUS) or contrast enhanced spectral mammography (CESM). These imaging techniques have been shown to be more sensitive than mammography at detecting cancers in dense breast tissue. Our hypothesis is that more cancers will be detected at an earlier stage with supplemental imaging.

Official Title
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Breast Screening - Risk Adaptive Imaging for Density

Conditions
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Breast Cancer

Intervention / Treatment
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* Diagnostic Test: ABUS
* Diagnostic Test: CESM
* Diagnostic Test: ABB-MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to give written informed consent Willing and able to comply with the scheduled study visits, tests and other procedures Female Screening mammogram that is either normal or being recalled for assessment Increased breast density identified on current screening mammogram examination (BIRADS C or D) If BIRADS C the reporting radiologist should use clinical judgement as to eligibility, there should be a high chance of a cancer being masked in this participant All BIRADS D will be eligible Aged 50-70 and eligible for 3-yearly NHS breast screening Exclusion Criteria: Known BRCA carrier or ≥50% risk of being a carrier Unable to give informed consent Breast implant(s) Unable to be followed-up for the study duration Current participation in another interventional breast screening trial (Including but not limited to MyPeBS) Participated in part A of the BRAID study Pregnant or breast feeding

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of Care<br>Control arm, no supplementary imaging is given. Participants have mammographic screening 3-yearly as per current standard of are. | |
| Active Comparator: Abbreviated MRI (ABB-MRI)<br>Supplementary imaging with abbreviated MRI at study entry and 18 months after baseline mammogram. | Diagnostic Test: ABB-MRI<br>* ABB-MRI is a shorter version of breast MRI. Standard T1W pre and post contrast images are acquired. A MIP and post-contrast T1 weighted image are read.<br>* Other names: Abbreviated Breast MRII;|
| Active Comparator: Automated Breast Ultrasound (ABUS)<br>Supplementary imaging with automated breast ultrasound at study entry and 18 months after baseline mammogram. | Diagnostic Test: ABUS<br>* Automated whole breast ultrasound (ABUS) is undertaken with a large transducer panel placed on the breast in three positions. Resultant images are combined to make a 3D image of the breast.<br>* Other names: Automated Breast Ultrasound;|
| Active Comparator: Contrast Enhanced Mammography (CESM)<br>Supplementary imaging with contrast enhanced spectral mammography at study entry and 18 months after baseline mammogram. | Diagnostic Test: CESM<br>* A high kV and a low kV image is taken in two standard views of each breast following the intravenous injection of an iodinated contrast agent.<br>* Other names: Contrast Enhanced Mammography;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cancer detection rate in each arm | All cancers (detected or interval) in each arm over a three year period will be collected. | 42 months after mammogram at study entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of stage II or worse cancers over the period of observation | size, lymph node status, metastatic status | 42 months after last participant entered | 
| The sensitivity and specificity of supplemental imaging with ABB-MRI, CESM and ABUS with standard 2D FFDM. | Analysis will include: Detection rate of all breast cancers, Detection rate of all breast cancers by stage; Detection rate of all breast cancers by biological type; Detection rate of all breast cancers by size; Recall rates at prevalent round | 6 months after mammogram at study entry | 
| The sensitivity and specificity of supplemental imaging with ABB-MRI, CESM and ABUS with standard 2D FFDM. | Analysis will include: Detection rate of all breast cancers, Detection rate of all breast cancers by stage; Detection rate of all breast cancers by biological type; Detection rate of all breast cancers by size; Recall rates | 21 months after mammogram at study entry | 
| The sensitivity and specificity of supplemental imaging with ABB-MRI, CESM and ABUS with standard 2D FFDM. | Analysis will include: Detection rate of all breast cancers, Detection rate of all breast cancers by stage; Detection rate of all breast cancers by biological type; Detection rate of all breast cancers by size; Recall rates at incident round; Interval cancer rate; Stage of interval cancers; Size of interval cancers | 42 months after last participant entered | 
| Reading time of each examination | Average time and range for each modality. (Seconds). | 1 year | 
| Automated breast density measurements compared with reader assessment | Percentage density. | Baseline | 
| The risk of developing breast cancer as assessed by the BOADICEA model | Percentage 5 year risk, percentage lifetime risk. | 72 months After last participant entered |