AgeX trials of extending the breast screening age range: study protocol for the follow-up phase (2025–2033)

Background In England, the NHS breast screening programme routinely invites women aged 50–70 years for triennial digital mammography. While screening may reduce breast cancer mortality, it may also lead to overdiagnosis and unnecessary treatment. In 2007, the UK Government announced an eventual extension of the screening age range to 47–73 years, but the balance of benefits and harms outside the existing age range was uncertain. To address this, AgeX began in 2009 and comprises two large cluster-randomised trials evaluating the effects of one additional breast screening in women aged 47–49 years and, separately, in women aged 71–73 years. Methods Between 2009 and 2020, approximately 2.8 million younger women and 1.7 million older women were randomised to be offered, or not offered, one additional screening invitation. Long-term follow-up continues through electronic linkage to routinely collected NHS records. The primary analyses are of breast cancer mortality, and main subsidiary analyses are of breast cancer incidence, treatment and health economic evaluation. The population for analyses will be restricted to approximately 2 million younger women and 1 million older women who, at randomisation, were of eligible age, alive, linkable to national records, without any history in national records of cancer or breast disease, and likely to accept screening based on previous attendance. All exclusions are unbiased, as they are based on information recorded before randomisation. Adherence-corrected analyses will estimate the effects of attending one additional screening at age 47–49 and, separately, at age 71–73. Parallel intention-to-treat analyses will assess the effects of being invited, irrespective of attendance. Analyses of incidence and treatment are planned for 2026. Interim analyses of breast cancer mortality (follow-up to December 2026) are planned for 2027–2028, with final analyses (follow-up to December 2031) in 2032–2033. Health economic analyses will accompany the final mortality results. Discussion AgeX will reliably assess the clinical- and cost-effectiveness of extending breast screening to younger and/or older women, and will inform future screening policy in the UK and in countries with similar screening programmes. Trial registration ClinicalTrials.gov NCT01081288. Registered on 04/03/2010; UK Clinical Study Registry ISRCTN33292440. Registered on 22/02/2010.