Abstract
Background
Screening for breast cancer produces benefits through cancers being detected earlier, thereby reducing premature deaths and the need for more intensive treatment. As with all screening, it can also produce harms such as false positive screening test results. One way to improve the ratio of benefits to harms is through risk-stratification. The main potential benefits of risk-stratified screening are via identifying women currently unaware that they are at increased risk, who can be offered more frequent screening and medicines for breast cancer prevention. However, it is unclear if these benefits would materialise in routine practice, whether additional harms would materialise and whether risk-stratification is cost-effective.
Objectives
Our aims were to develop a risk-stratification system, BC-Predict, and to evaluate its feasibility when delivered as part of the NHS Breast Screening Programme (NHSBSP). Specific objectives were to: (a) automate BC-Predict informatics systems and integrate into NHSBSP, (b) optimise to be acceptable to women offered it and healthcare professionals delivering it, (c) assess feasibility of BC-Predict, including estimates of benefits and harms, (d) identify likely cost-effectiveness, and (e) engage key stakeholders to consider how risk-stratification should be taken forward.
Design and Methods
The PROCAS2-Collator software was created to control the workflow of BC-Predict, and qualitative methods were used to develop patient-facing materials, care pathways and study procedures.
The main feasibility study involved women being offered BC-Predict as part of routine NHSBSP, with a comparison group of standard NHSBSP.
Setting and participants
BC-Predict was offered at seven screening sites (three screening centres), with the comparison standard NHSBSP organised by two sites (one screening centre), within North-West England. Participants were all women offered the NHSBSP at participating sites, with nested qualitative work with healthcare providers from the same screening centres..
Intervention
The BC-Predict risk-stratification system, offered to women when invited to the NHSBSP, calculated 10-year risk based on the Tyrer-Cuzick model, and produced risk feedback letters after negative screening test results were received. Women at high risk (≥8% 10-year) or moderate risk (≥5% to <8% 10-year) were thereby encouraged to make telephone appointments to discuss prevention and early detection options.
Main outcome measures
Uptake of BC-Predict and subsequent prevention and early detection offers. BC-Predict was costed using an NHS perspective, and a decision-analytic model-based cost-effectiveness analysis was technically verified with validation.
Results
BC-Predict was offered to 19,464 women, where 14,661 women attended screening (60.7%). Only 2,429 women (12.5%) who were eligible took up the offer of BC-Predict. Uptake was substantially higher when women were personally approached at the study site: 137/263 (52.1%). Attendance at the telephone risk appointments offered was also lower than expected: 80/197 (40.6%) of high-risk and 68/379 (17.9%) of moderate-risk women. Of those who took up risk appointments, 105/148 (71%) women received a prescription for preventive medication and 63/80 (79%) accepted additional mammography. The cost-effectiveness analysis indicated that risk-based screening using self-reported risk factors and mammographic density provided 0.004 incremental QALYs per woman screened at an additional cost of £42 when compared to 3 yearly screening, and hence was a better use of health care budgets.
A nested questionnaire study found no effects on general anxiety or cancer-related worry for women offered BC-Predict. Thematic analyses of qualitative interviews revealed women were positive about BC-Predict, with only transient increases in worry reported by high-risk women. Healthcare professionals who were involved with the implementation were generally enthusiastic about risk-stratified screening. The agenda-setting meeting identified a consensual view that risk-stratified screening is likely to happen eventually, and that there is a need to develop plans to prepare for it.
Limitations
The study was not randomised and was dramatically impacted by the COVID-19 pandemic with uptake of the study and of risk appointments in those identified as moderate or high risk almost certainly affected. As such, generalisability of the results will need to be reassessed after the results from the MyPeBS trial are available.
Conclusions
The present work suggests that risk-stratified screening for breast cancer is feasible, acceptable and likely to be a cost-effective use of the health care budget. Key stakeholders at all stages viewed risk-stratified screening as generally desirable and inevitable.
Future work
The MyPEBS trial has recruited over 50,000 women to examine effectiveness of risk-stratified screening at preventing later-stage (2+) breast cancers. It is timely to consider IT and workforce needs now, and how best to engage women, especially those who are currently underserved by the existing NHSBSP.
Study registration
The main BC-Predict feasibility study was registered with clinicaltrials.gov (NCT04359420).
Funding details
The project was funded by the National Institute for Health Research (NIHR) PROCAS2 programme and will be published in full in the NIHR Library.
Screening for breast cancer produces benefits through cancers being detected earlier, thereby reducing premature deaths and the need for more intensive treatment. As with all screening, it can also produce harms such as false positive screening test results. One way to improve the ratio of benefits to harms is through risk-stratification. The main potential benefits of risk-stratified screening are via identifying women currently unaware that they are at increased risk, who can be offered more frequent screening and medicines for breast cancer prevention. However, it is unclear if these benefits would materialise in routine practice, whether additional harms would materialise and whether risk-stratification is cost-effective.
Objectives
Our aims were to develop a risk-stratification system, BC-Predict, and to evaluate its feasibility when delivered as part of the NHS Breast Screening Programme (NHSBSP). Specific objectives were to: (a) automate BC-Predict informatics systems and integrate into NHSBSP, (b) optimise to be acceptable to women offered it and healthcare professionals delivering it, (c) assess feasibility of BC-Predict, including estimates of benefits and harms, (d) identify likely cost-effectiveness, and (e) engage key stakeholders to consider how risk-stratification should be taken forward.
Design and Methods
The PROCAS2-Collator software was created to control the workflow of BC-Predict, and qualitative methods were used to develop patient-facing materials, care pathways and study procedures.
The main feasibility study involved women being offered BC-Predict as part of routine NHSBSP, with a comparison group of standard NHSBSP.
Setting and participants
BC-Predict was offered at seven screening sites (three screening centres), with the comparison standard NHSBSP organised by two sites (one screening centre), within North-West England. Participants were all women offered the NHSBSP at participating sites, with nested qualitative work with healthcare providers from the same screening centres..
Intervention
The BC-Predict risk-stratification system, offered to women when invited to the NHSBSP, calculated 10-year risk based on the Tyrer-Cuzick model, and produced risk feedback letters after negative screening test results were received. Women at high risk (≥8% 10-year) or moderate risk (≥5% to <8% 10-year) were thereby encouraged to make telephone appointments to discuss prevention and early detection options.
Main outcome measures
Uptake of BC-Predict and subsequent prevention and early detection offers. BC-Predict was costed using an NHS perspective, and a decision-analytic model-based cost-effectiveness analysis was technically verified with validation.
Results
BC-Predict was offered to 19,464 women, where 14,661 women attended screening (60.7%). Only 2,429 women (12.5%) who were eligible took up the offer of BC-Predict. Uptake was substantially higher when women were personally approached at the study site: 137/263 (52.1%). Attendance at the telephone risk appointments offered was also lower than expected: 80/197 (40.6%) of high-risk and 68/379 (17.9%) of moderate-risk women. Of those who took up risk appointments, 105/148 (71%) women received a prescription for preventive medication and 63/80 (79%) accepted additional mammography. The cost-effectiveness analysis indicated that risk-based screening using self-reported risk factors and mammographic density provided 0.004 incremental QALYs per woman screened at an additional cost of £42 when compared to 3 yearly screening, and hence was a better use of health care budgets.
A nested questionnaire study found no effects on general anxiety or cancer-related worry for women offered BC-Predict. Thematic analyses of qualitative interviews revealed women were positive about BC-Predict, with only transient increases in worry reported by high-risk women. Healthcare professionals who were involved with the implementation were generally enthusiastic about risk-stratified screening. The agenda-setting meeting identified a consensual view that risk-stratified screening is likely to happen eventually, and that there is a need to develop plans to prepare for it.
Limitations
The study was not randomised and was dramatically impacted by the COVID-19 pandemic with uptake of the study and of risk appointments in those identified as moderate or high risk almost certainly affected. As such, generalisability of the results will need to be reassessed after the results from the MyPeBS trial are available.
Conclusions
The present work suggests that risk-stratified screening for breast cancer is feasible, acceptable and likely to be a cost-effective use of the health care budget. Key stakeholders at all stages viewed risk-stratified screening as generally desirable and inevitable.
Future work
The MyPEBS trial has recruited over 50,000 women to examine effectiveness of risk-stratified screening at preventing later-stage (2+) breast cancers. It is timely to consider IT and workforce needs now, and how best to engage women, especially those who are currently underserved by the existing NHSBSP.
Study registration
The main BC-Predict feasibility study was registered with clinicaltrials.gov (NCT04359420).
Funding details
The project was funded by the National Institute for Health Research (NIHR) PROCAS2 programme and will be published in full in the NIHR Library.
| Original language | English |
|---|---|
| Journal | NIHR Journal Library |
| Publication status | Accepted/In press - 2 Jun 2025 |