English Mammography Screening Outcomes by Age, Frequency and Test Threshold

Breast Cancer Clinical Trial

— ATHENA-M  

Official title:

Observational Study of Age, Test THreshold and Frequency on English NAtional Mammography Screening Outcomes (ATHENA-M)

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05247463
• Other study ID #: SOC.03/20-21
• Status: Enrolling by invitation
• Start date: January 1, 2021
• Est. completion date: December 30, 2024

Study information

• Verified date: December 2023
• Source: University of Warwick
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. This observational study links breast cancer screening, cancer registry and mortality registration data to answer these questions.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 10000000
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 47 Years to 73 Years

Eligibility

Inclusion Criteria:

• Women invited for breast cancer screening by the English NHS Breast Screening Programme

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Breast Cancer

Intervention

Other:
• Increase in upper age of eligibility for breast cancer screening from 64 to 70
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 length
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

Diagnostic Test:
• Screening test threshold
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.

Locations

Country	Name	City	State
United Kingdom	University of Warwick	Coventry	Warwickshire

Sponsors (3)

Lead Sponsor	Collaborator
University of Warwick	University of Birmingham, University of Bristol

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Breast Cancer Specific Mortality	Breast Cancer Specific Mortality	Cumulative incidence of breast cancer specific mortality over all follow-up time (up to maximum 30 years)
Primary	Breast Cancer Specific Mortality	Breast Cancer Specific Mortality	10 year follow up of particular importance to match previous systematic review of results
Primary	Breast Cancer Specific Mortality	Breast Cancer Specific Mortality	13 year follow up of particular importance to match previous systematic review of results
Primary	All cause mortality	All cause mortality	Cumulative incidence of all-cause mortality over all follow-up time (up to maximum 30 years)
Primary	All cause mortality	All cause mortality	10 year follow up of particular importance to match breast cancer mortality
Primary	All cause mortality	All cause mortality	13 year follow up of particular importance to match breast cancer mortality
Primary	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	Cumulative incidence of cancer over all follow-up time (up to maximum 30 years)
Primary	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	10 year follow up of particular importance to match breast cancer mortality
Primary	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	13 year follow up of particular importance to match breast cancer mortality
Primary	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	For breast cancers detected at any point during follow-up (up to a maximum 30 years)
Primary	Treatment Received	Breast Cancer Treatment received (as a proxy for treatment associated morbidity)	Within 1 year of diagnosis
Primary	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	At point of screening episode
Secondary	Interval cancers	Biopsy-proven breast cancers detected after symptomatic referral during the time interval between screening mammograms.	Up to 3 years after the screening appointment
Secondary	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	At screening episode
Secondary	Screen detected cancer characteristics	(DCIS vs invasive, grade, size, nodes involved, cancer type, hormonal status, Nottingham Prognostic Index, distant metastasis	At screening episode