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Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial - 02/09/20

Doi : 10.1016/S1470-2045(20)30398-3 
Stephen W Duffy, ProfMSc a, , , Daniel Vulkan, MSc a, , Howard Cuckle, ProfDPhil b, Dharmishta Parmar, BA a, Shama Sheikh, MSc c, Robert A Smith, PhD d, Andrew Evans, ProfFRCR e, Oleg Blyuss, PhD f, g, Louise Johns, PhD c, Ian O Ellis, ProfMD h, Jonathan Myles, PhD a, Peter D Sasieni, ProfPhD c, , Sue M Moss, ProfPhD a,
a Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK 
b Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 
c Cancer Prevention Group, King’s College London, London, UK 
d American Cancer Society, Atlanta, GA, USA 
e Division of Cancer Research, University of Dundee, Dundee, UK 
f School of Physics, Astronomy, and Mathematics, University of Hertfordshire, Hatfield, UK 
g Department of Paediatrics and Paediatric Infectious Diseases, Sechenov First Moscow State Medical University, Moscow, Russia 
h Division of Cancer and Stem Cells, University of Nottingham, Nottingham, UK 

* Correspondence to: Prof Stephen W Duffy, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London EC1M 6BQ, UK Centre for Cancer Prevention Wolfson Institute of Preventive Medicine Queen Mary University of London London EC1M 6BQ UK

Summary

Background

The appropriate age range for breast cancer screening remains a matter of debate. We aimed to estimate the effect of mammographic screening at ages 40–48 years on breast cancer mortality.

Methods

We did a randomised, controlled trial involving 23 breast screening units across Great Britain. We randomly assigned women aged 39–41 years, using individual randomisation, stratified by general practice, in a 1:2 ratio, to yearly mammographic screening from the year of inclusion in the trial up to and including the calendar year that they reached age 48 years (intervention group), or to standard care of no screening until the invitation to their first National Health Service Breast Screening Programme (NHSBSP) screen at approximately age 50 years (control group). Women in the intervention group were recruited by postal invitation. Women in the control group were unaware of the study. The primary endpoint was mortality from breast cancers (with breast cancer coded as the underlying cause of death) diagnosed during the intervention period, before the participant’s first NHSBSP screen. To study the timing of the mortality effect, we analysed the results in different follow-up periods. Women were included in the primary comparison regardless of compliance with randomisation status (intention-to-treat analysis). This Article reports on long-term follow-up analysis. The trial is registered with the ISRCTN registry, ISRCTN24647151.

Findings

160 921 women were recruited between Oct 14, 1990, and Sept 24, 1997. 53 883 women (33·5%) were randomly assigned to the intervention group and 106 953 (66·5%) to the control group. Between randomisation and Feb 28, 2017, women were followed up for a median of 22·8 years (IQR 21·8–24·0). We observed a significant reduction in breast cancer mortality at 10 years of follow-up, with 83 breast cancer deaths in the intervention group versus 219 in the control group (relative rate [RR] 0·75 [95% CI 0·58–0·97]; p=0·029). No significant reduction was observed thereafter, with 126 deaths versus 255 deaths occurring after more than 10 years of follow-up (RR 0·98 [0·79–1·22]; p=0·86).

Interpretation

Yearly mammography before age 50 years, commencing at age 40 or 41 years, was associated with a relative reduction in breast cancer mortality, which was attenuated after 10 years, although the absolute reduction remained constant. Reducing the lower age limit for screening from 50 to 40 years could potentially reduce breast cancer mortality.

Funding

National Institute for Health Research Health Technology Assessment programme.

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© 2020  The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 21 - N° 9

P. 1165-1172 - septembre 2020 Retour au numéro
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