Background
The UK NHS routinely offers all women free triennial 2-view digital mammographic breast screening at ages 50-70, and any NHS treatment arising from this is also free. The advantages and disadvantages of starting at a somewhat earlier age are uncertain. Likewise, there is uncertainty about the advantages and disadvantages of continuing to a somewhat later age.
In 2007, the Prime Minister announced eventual extension of NHS breast screening from ages 50-70 to 47-731, but it was unclear when this would begin. This offered an opportunity for AgeX to obtain large-scale randomised evidence about the effects of one additional screening.
During 2009-20 Age X has randomly allocated 20,000 clusters of women aged about 47-49 to be offered, or not, one additional screening invitation and, separately, 20,000 clusters of women aged 71-73 to be offered, or not, one additional screening invitation.
Follow-up is only through linkage to routine records held centrally by NHS England, which will help assess the effects of one additional screening on breast cancer mortality (the primary endpoint), on breast cancer incidence, and on the eventual use of radiotherapy and chemotherapy.
In 2011, the Government deferred the date for extending the screening age range2. In 2012, an independent panel set up by the Department of Health and the charity Cancer Research UK reported “The UK breast screening programmes [at ages about 50-70] confer significant benefit and should continue…. The impact of breast screening [outside this age range] is very uncertain. The Panel supports the principle of the ongoing trial[s] in the UK [AgeX] for randomising women under age 50 and above age 70 to be invited for breast screening”3.
In 2013 Public Health England became responsible for government screening programmes, and stated that final decisions about extension of the age range would await the emergence of reliable evidence of its effects, and in 2018 an independent enquiry into the nationwide delivery of breast screening had reported that AgeX should continue “until its planned end in 2026”4, with formal Government statements in both Houses of Parliament then accepting this recommendation5,6. In 2021, NHS England replaced Public Health England.
Although AgeX randomisation was to continue until 2026, in March 2020 it ended following the suspension of all breast screening due to COVID. Interim and final analyses will report breast cancer mortality to 12.2026 and to 12.2031. This ensures the eventual length of follow-up will be about one or two decades (depending on the year of randomisation).
The design and follow-up of AgeX remain similar to what was envisaged in the linked protocol for the randomisation phase, with the few differences outlined in Annex 1. This protocol is for the 2025-33 follow-up phase of AgeX, after randomisation of 4.5 million women during 2009-20 and consolidation of the database during 2021-24. This consolidation included identifying for the main analyses the 3 million women who had been eligible and were linkable to NHS England datasets, with no prior record there of cancer or breast disease, and who were considered likely to attend screening if invited (as they had attended their previous breast or cervical screening invitation). Since AgeX began, the dataset has been held securely, with access to any personal identifiers strictly restricted even within the study team (Annex 2).