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

Stephen W. Duffy; Daniel Vulkan; Howard Cuckle; Dharmishta Parmar; Shama Sheikh; Robert A. Smith; Andrew Evans; Oleg Blyuss; Louise Johns; Ian O. Ellis; Jonathan Myles; Peter D. Sasieni; Sue M. Moss

doi:10.1016/S1470-2045(20)30398-3

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

Stephen W. Duffy^*, Daniel Vulkan, Howard Cuckle, Dharmishta Parmar, Shama Sheikh, Robert A. Smith, Andrew Evans, Oleg Blyuss, Louise Johns, Ian O. Ellis, Jonathan Myles, Peter D. Sasieni, Sue M. Moss

^*Corresponding author for this work

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Abstract

BackgroundThe 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.MethodsWe 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.Findings160 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).InterpretationYearly 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.FundingNational Institute for Health Research Health Technology Assessment programme.

Original language	English
Pages (from-to)	1165-1172
Number of pages	8
Journal	The Lancet Oncology
Volume	21
Issue number	9
Early online date	12 Aug 2020
DOIs	https://doi.org/10.1016/S1470-2045(20)30398-3
Publication status	Published - 1 Sept 2020

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Duffy, S. W., Vulkan, D., Cuckle, H., Parmar, D., Sheikh, S., Smith, R. A., Evans, A., Blyuss, O., Johns, L., Ellis, I. O., Myles, J., Sasieni, P. D., & Moss, S. M. (2020). Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial. The Lancet Oncology, 21(9), 1165-1172. https://doi.org/10.1016/S1470-2045(20)30398-3

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title = "Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial",

abstract = "BackgroundThe 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.MethodsWe 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.Findings160 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).InterpretationYearly 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.FundingNational Institute for Health Research Health Technology Assessment programme.",

author = "Duffy, {Stephen W.} and Daniel Vulkan and Howard Cuckle and Dharmishta Parmar and Shama Sheikh and Smith, {Robert A.} and Andrew Evans and Oleg Blyuss and Louise Johns and Ellis, {Ian O.} and Jonathan Myles and Sasieni, {Peter D.} and Moss, {Sue M.}",

year = "2020",

month = sep,

day = "1",

doi = "10.1016/S1470-2045(20)30398-3",

language = "English",

volume = "21",

pages = "1165--1172",

journal = "The Lancet Oncology",

issn = "1470-2045",

publisher = "Lancet Publishing Group",

number = "9",

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Duffy, SW, Vulkan, D, Cuckle, H, Parmar, D, Sheikh, S, Smith, RA, Evans, A, Blyuss, O, Johns, L, Ellis, IO, Myles, J, Sasieni, PD & Moss, SM 2020, 'Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial', The Lancet Oncology, vol. 21, no. 9, pp. 1165-1172. https://doi.org/10.1016/S1470-2045(20)30398-3

TY - JOUR

T1 - Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial)

T2 - final results of a randomised, controlled trial

AU - Duffy, Stephen W.

AU - Vulkan, Daniel

AU - Cuckle, Howard

AU - Parmar, Dharmishta

AU - Sheikh, Shama

AU - Smith, Robert A.

AU - Evans, Andrew

AU - Blyuss, Oleg

AU - Johns, Louise

AU - Ellis, Ian O.

AU - Myles, Jonathan

AU - Sasieni, Peter D.

AU - Moss, Sue M.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - BackgroundThe 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.MethodsWe 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.Findings160 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).InterpretationYearly 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.FundingNational Institute for Health Research Health Technology Assessment programme.

AB - BackgroundThe 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.MethodsWe 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.Findings160 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).InterpretationYearly 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.FundingNational Institute for Health Research Health Technology Assessment programme.

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DO - 10.1016/S1470-2045(20)30398-3

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SN - 1470-2045

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JO - The Lancet Oncology

JF - The Lancet Oncology

IS - 9

ER -

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

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