English Mammography Screening Outcomes by Age, Frequency and Test Threshold

• Conditions: Breast Cancer
• Interventions: Other: Increase in upper age of eligibility for breast cancer screening from 64 to 70; Other: Screening round length; Diagnostic Test: Screening test threshold

• Registration Number: NCT05247463
• Lead Sponsor: University of Warwick

Brief 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.

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 Timeline

• Study Start: 2021-01-01
• Study First Submitted: 2022-01-27
• Study First Submitted QC: 2022-02-09
• Study First Posted: 2022-02-18
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-11
• Last Update Posted: 2023-12-12
• Primary Completion: 2024-12-30
• Study Completion: 2024-12-30

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: Female
• Target Recruitment: 10000000

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Women invited to Breast Cancer Screening in England	Increase in upper age of eligibility for breast cancer screening from 64 to 70	Women invited to Breast Cancer Screening in England up to 31st March 2018
Women attending Breast Cancer Screening in England	Screening round length	Women attending mammography screening to examine the effect of screening test threshold on outcomes, up to 31st March 2018
Women attending Breast Cancer Screening in England	Screening test threshold	Women attending mammography screening to examine the effect of screening test threshold on outcomes, up to 31st March 2018

Primary Outcome Measures

Name	Time	Method
Overdiagnosis	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	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	Within 1 year of diagnosis	Breast Cancer Treatment received (as a proxy for treatment associated morbidity)
Breast Cancer Specific Mortality	13 year follow up of particular importance to match previous systematic review of results	Breast Cancer Specific Mortality
False positive recall to assessment	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
All cause mortality	13 year follow up of particular importance to match breast cancer mortality	All cause mortality

Secondary Outcome Measures

Name	Time	Method
Cancers detected at screening	At screening episode	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
Interval cancers	Up to 3 years after the screening appointment	Biopsy-proven breast cancers detected after symptomatic referral during the time interval between screening mammograms.
Screen detected cancer characteristics	At screening episode	(DCIS vs invasive, grade, size, nodes involved, cancer type, hormonal status, Nottingham Prognostic Index, distant metastasis

Trial Locations

Locations (1)

University of Warwick; 🇬🇧 Coventry, Warwickshire, United Kingdom