Breast CancerATHENA-MNCT05247463
English Mammography Screening Outcomes by Age, Frequency and Test Threshold
An observational study of Breast Cancer, run by University of Warwick at 1 site in United Kingdom.
Trial summary
Breast cancer screening involves taking mammograms (x-rays) of women's breasts to search for signs of cancer. This study investigates the impact of test threshold, screening interval (frequency) and age of eligibility on intermediate outcomes, and health outcomes such as mortality and morbidity. Read more about this study
- Who is it for?
- Ages 47 to 73 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Increase in upper age of eligibility for breast cancer screening from 64 to 70, Screening round length and Screening test threshold
- How many people
- 10,000,000 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jan 2021to 30 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 47 to 73 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Women invited for a Breast Cancer Screening appointment in England between 1st January 1988 and 31st March 2018. For test threshold and screening interval data this is further limited to women attending at least one breast screening appointment meeting the age and date eligibility requirements. The population will be further limited to women invited for breast cancer screening after 1st January 1998, if accurate data linkage cannot be achieved before this date in the absence of a unique identifier (before the widespread implementation of NHS number)
Who may be able to join
- Women invited for breast cancer screening by the English NHS Breast Screening Programme
Who cannot join
- Missing or corrupted data for NHS number, so linkage between databases is not possible
- For analysis of test threshold and screening interval: women who did not attend routine English NHS Breast screening service within the specified date and age range, even if they attended symptomatic breast cancer services, high risk (family history) breast screening services, or if they were referred for mammograms by their general practitioner
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Warwick
Coventry, Warwickshire, CV47AL
About this study
Official title: Observational Study of Age, Test THreshold and Frequency on English NAtional Mammography Screening Outcomes (ATHENA-M)
Breast cancer screening involves taking mammograms (x-rays) of women's breasts to search for signs of cancer. This study investigates the impact of test threshold, screening interval (frequency) and age of eligibility on intermediate outcomes, and health outcomes such as mortality and morbidity. This observational study links breast cancer screening, cancer registry and mortality registration data to answer these questions.
Read the detailed description
Breast cancer screening involves taking mammograms (x-rays) of women's breasts to search for signs of cancer. Different countries give different versions of breast screening, because there is no clear evidence which is best. This study investigates the effect of three variations to breast screening on outcomes for women screened.
Firstly, the test threshold. When radiologists examine the women's mammograms it is often not clear whether cancer is present. The test threshold means the tendency of radiologists to recall more or fewer women for further tests. In England overall 4% of women are recalled for further tests because their mammograms show suspicious signs, but different radiologists vary between 2% and 10%. This study investigates how recalling different proportions of women affects their long term outcomes.
Secondly the interval between screening invitations. In the UK breast screening is every 3 years, which is the longest time between screens in the world. In the US it is every year or 2 years and in Europe every 2 years. This study uses the natural variation in English screening interval to investigate the impact on women's outcomes.
Thirdly the age women are invited for breast screening. The NHS Cancer Plan in England resulted in extension of the upper age limit of eligibility for breast cancer screening from 64 to 70. This study investigates the change on women's outcomes.
The primary outcomes are health outcomes or close approximations, such as mortality, overdiagnosis of cancer which would never have caused harm, stage shift in cancer diagnosis, treatment (to reflect treatment associated morbidity), and false positive recall to assessment (which is known to induce anxiety). Secondary outcomes are intermediate outcomes with known but more proximal links to health outcomes: number of cancers detected at screening and their characteristics, and number of interval cancers detected between screening rounds.
This is an observational study linking women's screening records to cancer registry and mortality records from 1988 to 2018.
This observational study began on 1st January 2021, building on the POSTBOx study (NCT04365114). POSTBOx evaluates the impact of one or two readers on women's outcomes, POSTBOx primary outcomes 4 and 5 and secondary outcome 1 were dependent on obtaining follow up funding, which was achieved in this ATHENA-M project. The ATHENA-M funding also adds two additional exposures (screening interval and age of eligibility), and expands analysis of the test threshold exposure. Both projects were significantly delayed in data linkage and transfer, the investigators expect complete data transfer to the analysis team at Warwick between February and April 2022.
- Conditions
- Breast Cancer
- Being tested
- Increase in upper age of eligibility for breast cancer screening from 64 to 70, Screening round length, Screening test threshold
- Keywords
- Screening, Observational
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Increase in upper age of eligibility for breast cancer screening from 64 to 70Other
The upper age limit of eligibility for Breast Cancer Screening increased in England from 64 to 70 as a result of the NHS Cancer Plan, so women were offered an additional 2 rounds of screening.
Screening round lengthOther
The target round length (frequency) of breast cancer screening in England is every 3 years. However in practice there is variability in this due to local centre capacity. The exposures are round lengths of approximately 2 years and approximately 3 years
Screening test thresholdDiagnostic test
Radiologists and equivalent health professionals examine women's screening mammograms for potential signs of cancer, and recall some women for further diagnostic tests. Each has a different test threshold for recall, characterised by the proportion of previous cases that they have recalled.
| Study group | Role | What they receive |
|---|---|---|
| Women invited to Breast Cancer Screening in England | Women invited to Breast Cancer Screening in England up to 31st March 2018 Receives: Other: Increase in upper age of eligibility for breast cancer screening from 64 to 70 | |
| Women attending Breast Cancer Screening in England | Women attending mammography screening to examine the effect of screening test threshold on outcomes, up to 31st March 2018 Receives: Other: Screening round length; Diagnostic Test: Screening test threshold |
What is being measured
The primary outcome is the main question the study is designed to answer.
Breast Cancer Specific Mortality
Breast Cancer Specific Mortality
Measured: Cumulative incidence of breast cancer specific mortality over all follow-up time (up to maximum 30 years)
Breast Cancer Specific Mortality
Breast Cancer Specific Mortality
Measured: 10 year follow up of particular importance to match previous systematic review of results
Breast Cancer Specific Mortality
Breast Cancer Specific Mortality
Measured: 13 year follow up of particular importance to match previous systematic review of results
All cause mortality
All cause mortality
Measured: Cumulative incidence of all-cause mortality over all follow-up time (up to maximum 30 years)
All cause mortality
All cause mortality
Measured: 10 year follow up of particular importance to match breast cancer mortality
All cause mortality
All cause mortality
Measured: 13 year follow up of particular importance to match breast cancer mortality
Overdiagnosis
Overdiagnosis of breast cancer which would not have been detected symptomatically using compensatory drop method, (difference between cumulative incidence of cancer (screening and symptomatic) between exposure groups
Measured: Cumulative incidence of cancer over all follow-up time (up to maximum 30 years)
Overdiagnosis
Overdiagnosis of breast cancer which would not have been detected symptomatically using compensatory drop method, (difference between cumulative incidence of cancer (screening and symptomatic) between exposure groups
Measured: 10 year follow up of particular importance to match breast cancer mortality
Overdiagnosis
Overdiagnosis of breast cancer which would not have been detected symptomatically using compensatory drop method, (difference between cumulative incidence of cancer (screening and symptomatic) between exposure groups
Measured: 13 year follow up of particular importance to match breast cancer mortality
Stage Shift
Difference in prognostic indicators (DCIS vs invasive, grade, size, nodes involved, cancer type, hormonal status, Nottingham Prognostic Index, distant metastasis) between exposure groups, including both symptomatically and screen detected cancers
Measured: For breast cancers detected at any point during follow-up (up to a maximum 30 years)
Treatment Received
Breast Cancer Treatment received (as a proxy for treatment associated morbidity)
Measured: Within 1 year of diagnosis
False positive recall to assessment
Proportion of women recalled for further tests from their screening mammogram, in whom those further tests did not detect breast cancer
Measured: At point of screening episode
Secondary outcomes (3)
Interval cancers
Biopsy-proven breast cancers detected after symptomatic referral during the time interval between screening mammograms.
Measured: Up to 3 years after the screening appointment
Cancers detected at screening
Number of biopsy proven cancers detected at screening (• Definition includes any invasive cancer or Ductal Carcinoma in situ (DCIS) or Lobular Carcinoma in Situ (LCIS) of the breast, using standard definition of cancer registry and screening programme) with subgroup with invasive cancer only also reported
Measured: At screening episode
Screen detected cancer characteristics
(DCIS vs invasive, grade, size, nodes involved, cancer type, hormonal status, Nottingham Prognostic Index, distant metastasis
Measured: At screening episode
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2022
- Study start1 Jan 2021
- Primary completion30 Dec 2024 (estimated)
- Study completion30 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 10,000,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Warwick
- Sponsor type
- University, hospital or other
- Collaborators
- University of Birmingham, University of Bristol
- Responsible party
- Principal investigator, Sian Taylor-Phillips, University of Warwick
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05247463
- Sponsor's protocol ID
- SOC.03/20-21
- Acronym
- ATHENA-M
- Status last verified
- Dec 2023
- First submitted
- 27 Jan 2022
- Last updated
- 12 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The investigators do not have Office for Data Release permissions to share these data more widely, but can assist other researchers in applying for access.
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Study of Age, Test THreshold and Frequency on English NAtional Mammography Screening Outcomes (ATHENA-M)
- ClinicalTrials.gov ID
- NCT05247463
- Acronym / sponsor ID
- ATHENA-M / SOC.03/20-21
- Conditions
- Breast Cancer
- Keywords
- Screening, Observational
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 10,000,000 participants (estimated)
- Lead sponsor
- University of WarwickUniversity, hospital or other
- Collaborators
- University of Birmingham, University of Bristol
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 30 Dec 2024 (estimated)
- Study completion
- 30 Dec 2024 (estimated)
- First posted
- 18 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Breast cancer screening involves taking mammograms (x-rays) of women's breasts to search for signs of cancer. This study investigates the impact of test threshold, screening interval (frequency) and age of eligibility on intermediate outcomes, and health outcomes such as mortality and morbidity. This observational study links breast cancer screening, cancer registry and mortality registration data to answer these questions.
Detailed description
Breast cancer screening involves taking mammograms (x-rays) of women's breasts to search for signs of cancer. Different countries give different versions of breast screening, because there is no clear evidence which is best. This study investigates the effect of three variations to breast screening on outcomes for women screened.
Firstly, the test threshold. When radiologists examine the women's mammograms it is often not clear whether cancer is present. The test threshold means the tendency of radiologists to recall more or fewer women for further tests. In England overall 4% of women are recalled for further tests because their mammograms show suspicious signs, but different radiologists vary between 2% and 10%. This study investigates how recalling different proportions of women affects their long term outcomes.
Secondly the interval between screening invitations. In the UK breast screening is every 3 years, which is the longest time between screens in the world. In the US it is every year or 2 years and in Europe every 2 years. This study uses the natural variation in English screening interval to investigate the impact on women's outcomes.
Thirdly the age women are invited for breast screening. The NHS Cancer Plan in England resulted in extension of the upper age limit of eligibility for breast cancer screening from 64 to 70. This study investigates the change on women's outcomes.
The primary outcomes are health outcomes or close approximations, such as mortality, overdiagnosis of cancer which would never have caused harm, stage shift in cancer diagnosis, treatment (to reflect treatment associated morbidity), and false positive recall to assessment (which is known to induce anxiety). Secondary outcomes are intermediate outcomes with known but more proximal links to health outcomes: number of cancers detected at screening and their characteristics, and number of interval cancers detected between screening rounds.
This is an observational study linking women's screening records to cancer registry and mortality records from 1988 to 2018.
This observational study began on 1st January 2021, building on the POSTBOx study (NCT04365114). POSTBOx evaluates the impact of one or two readers on women's outcomes, POSTBOx primary outcomes 4 and 5 and secondary outcome 1 were dependent on obtaining follow up funding, which was achieved in this ATHENA-M project. The ATHENA-M funding also adds two additional exposures (screening interval and age of eligibility), and expands analysis of the test threshold exposure. Both projects were significantly delayed in data linkage and transfer, the investigators expect complete data transfer to the analysis team at Warwick between February and April 2022.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Women invited to Breast Cancer Screening in England | – | Other: Increase in upper age of eligibility for breast cancer screening from 64 to 70Women invited to Breast Cancer Screening in England up to 31st March 2018 |
| Women attending Breast Cancer Screening in England | – | Other: Screening round length, Diagnostic Test: Screening test thresholdWomen attending mammography screening to examine the effect of screening test threshold on outcomes, up to 31st March 2018 |
Who may qualify
- Ages
- 47 to 73 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Women invited for a Breast Cancer Screening appointment in England between 1st January 1988 and 31st March 2018. For test threshold and screening interval data this is further limited to women attending at least one breast screening appointment meeting the age and date eligibility requirements. The population will be further limited to women invited for breast cancer screening after 1st January 1998, if accurate data linkage cannot be achieved before this date in the absence of a unique identifier (before the widespread implementation of NHS number)
Key inclusion criteria (1 listed)
- Women invited for breast cancer screening by the English NHS Breast Screening Programme
Key exclusion criteria (2 listed)
- Missing or corrupted data for NHS number, so linkage between databases is not possible
- For analysis of test threshold and screening interval: women who did not attend routine English NHS Breast screening service within the specified date and age range, even if they attended symptomatic breast cancer services, high risk (family history) breast screening services, or if they were referred for mammograms by their general practitioner
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Increase in upper age of eligibility for breast cancer screening from 64 to 70The upper age limit of eligibility for Breast Cancer Screening increased in England from 64 to 70 as a result of the NHS Cancer Plan, so women were offered an additional 2 rounds of screening. | Other | Women invited to Breast Cancer Screening in England |
| Screening round lengthThe target round length (frequency) of breast cancer screening in England is every 3 years. However in practice there is variability in this due to local centre capacity. The exposures are round lengths of approximately 2 years and approximately 3 years | Other | Women attending Breast Cancer Screening in England |
| Screening test thresholdRadiologists and equivalent health professionals examine women's screening mammograms for potential signs of cancer, and recall some women for further diagnostic tests. Each has a different test threshold for recall, characterised by the proportion of previous cases that they have recalled. | Diagnostic test | Women attending Breast Cancer Screening in England |
Primary outcome
Breast Cancer Specific Mortality
Time frame: Cumulative incidence of breast cancer specific mortality over all follow-up time (up to maximum 30 years)
Breast Cancer Specific Mortality
Breast Cancer Specific Mortality
Time frame: 10 year follow up of particular importance to match previous systematic review of results
Breast Cancer Specific Mortality
Breast Cancer Specific Mortality
Time frame: 13 year follow up of particular importance to match previous systematic review of results
Breast Cancer Specific Mortality
All cause mortality
Time frame: Cumulative incidence of all-cause mortality over all follow-up time (up to maximum 30 years)
All cause mortality
All cause mortality
Time frame: 10 year follow up of particular importance to match breast cancer mortality
All cause mortality
All cause mortality
Time frame: 13 year follow up of particular importance to match breast cancer mortality
All cause mortality
Overdiagnosis
Time frame: Cumulative incidence of cancer over all follow-up time (up to maximum 30 years)
Overdiagnosis of breast cancer which would not have been detected symptomatically using compensatory drop method, (difference between cumulative incidence of cancer (screening and symptomatic) between exposure groups
Overdiagnosis
Time frame: 10 year follow up of particular importance to match breast cancer mortality
Overdiagnosis of breast cancer which would not have been detected symptomatically using compensatory drop method, (difference between cumulative incidence of cancer (screening and symptomatic) between exposure groups
Overdiagnosis
Time frame: 13 year follow up of particular importance to match breast cancer mortality
Overdiagnosis of breast cancer which would not have been detected symptomatically using compensatory drop method, (difference between cumulative incidence of cancer (screening and symptomatic) between exposure groups
Stage Shift
Time frame: For breast cancers detected at any point during follow-up (up to a maximum 30 years)
Difference in prognostic indicators (DCIS vs invasive, grade, size, nodes involved, cancer type, hormonal status, Nottingham Prognostic Index, distant metastasis) between exposure groups, including both symptomatically and screen detected cancers
Treatment Received
Time frame: Within 1 year of diagnosis
Breast Cancer Treatment received (as a proxy for treatment associated morbidity)
False positive recall to assessment
Time frame: At point of screening episode
Proportion of women recalled for further tests from their screening mammogram, in whom those further tests did not detect breast cancer
3 secondary outcomes
Interval cancers
Time frame: Up to 3 years after the screening appointment
Cancers detected at screening
Time frame: At screening episode
Screen detected cancer characteristics
Time frame: At screening episode
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2023.
- Individual participant dataSharing planned: No. The investigators do not have Office for Data Release permissions to share these data more widely, but can assist other researchers in applying for access.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer, run by University of Warwick at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Breast Cancer Specific Mortality (time frame: Cumulative incidence of breast cancer specific mortality over all follow-up time (up to maximum 30 years)). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2023.