Title: Long-term follow up of a trial of annual mammographic screening from age 40
Funder: Department of Health and Social Care

Abstract: This project involves the long-term follow-up of an individual randomised controlled trial, in which 160,921 women aged 40-41 were randomised in the ratio 2:1 to an intervention arm invited to annual mammographic screening until age 48, and to a control arm receiving usual care. There were 23 participating centres in England, Wales and Scotland. Women in both arms become eligible for screening in the NHS Breast Screening Programme (NHSBSP) from age 50. Mammography in the trial was by two views at first screen, and by single view at subsequent screens unless otherwise indicated. Analogue mammography was used throughout the trial; digital mammography is now being introduced in the NHSBSP, and may potentially improve sensitivity. All women in this trial have been flagged at the NHS central register (NHSCR), and more than 99.9% successfully traced. This provides data on all cancer registrations and deaths, including data and underlying coded cause of death, and also on emigrations. The majority of these data are supplied electronically. The primary outcome measures will be breast cancer mortality, restricted to deaths in cases diagnosed after trial entry, and based on underlying cause of death from the death certificate, and the cumulative incidence of invasive and in situ breast cancer. We will analyse the risk of breast cancer mortality in the intervention arm relative to the control arm, and the reduction in absolute risk. The latter allows the 'number needed to be invited' and 'number need to be screened' to be calculated, and provide a comparison of cost-effectiveness with screening at other ages. The cumulative incidence of breast cancer will allow the extent of over-diagnosis due to screening to be measured, as well as any potential shift from invasive to in-situ disease.

Lay abstract: Breast cancer is the most common cause of death from cancer in women at ages 35-54 in the UK. The NHS breast screening programme (NHSBSP) currently invites women aged 50-70 years for screening by mammography; the age range is being extended to 47-73 years. The original decision to offer screening from age 50 was based on evidence then available from randomised trials which did not show clear evidence of a benefit of screening at younger ages. Debate about the value of screening women in their 40's continues in the academic and popular press. The present trial was uniquely designed to determine the additional benefit of annual mammographic screening from age 40 in reducing deaths from breast cancer. The trial was conducted in 23 screening units in the UK, and fieldwork was completed in 2005. The first mortality results from the trial did not show a significant reduction in breast cancer deaths in women offered screening. However long term follow up is essential in order to determine the full effect of this screening on future breast cancer incidence and mortality. Screening has potential harms as well as benefits, including the possibility that breast cancers will be found by screening that would not otherwise have been diagnosed during a woman's lifetime. The long-term follow-up of this trial with data on breast cancer registrations and deaths in trial participants. will allow the effect of screening in the trial on breast cancer deaths up to age 60 to be determined, the cost-effectiveness to be compared with that of screening at older ages, and the extent of any over-diagnosis of breast cancer to be estimated. Follow up to the end of 2017 will provide data on all women in the trial up to age 60.

Research activity codes: 4.4 POPULATION SCREENING;6.3 MEDICAL DEVICES
Health categories: CANCER AND NEOPLASMS