Stephen W. Duffy, MSc

As reported in The Lancet Oncology by Stephen W. Duffy, MSc, of the Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, and colleagues, final results of the UK Age Trial show that initiation of annual mammography screening for breast cancer at age 40 was associated with a significant reduction in breast cancer mortality at 10 years compared with screening beginning at age 50 years, with the preventive benefit being attenuated thereafter.¹

As stated by the investigators, “The United Kingdom, along with many other countries, has a breast cancer screening programme offering mammography to women aged 50–70 years every 3 years. There remains uncertainty as to the appropriate age at which to start screening, specifically about whether to screen women younger than 50 years.”

Study Details

In the study, 160,836 women aged 39 to 41 years were randomly assigned 1:2 between October 1990 and September 1997 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, n = 53,833) or to standard care of no screening until invitation to their first National Health Service Breast Screening Programme (NHSBSP) screen at approximately age 50 years (control group, n = 106,953). Women in the control group were not aware of the study. Participants were flagged with the National Health Service Central Register, with investigators being notified of all breast cancers, breast cancer deaths, and deaths from all other causes through February 2017. The primary endpoint was mortality from breast cancer diagnosed during the intervention period up to immediately before participants’ first NHSBSP screen in the intention-to-treat population.

Breast Cancer Mortality

Between randomization and February 2017, participants had a median follow-up of 22.8 years. The average screening participation rate in the intervention group was approximately 69%.

In the primary analysis, including cancers diagnosed in the intervention period up to immediately before the first NHSBSP screening, there were 83 breast cancer deaths in the intervention group vs 219 in the control group at 10 years (relative rate [RR] = 0.75, 95% confidence interval [CI] = 0.58–0.97; P = .029). During follow-up after 10 years, there were 126 deaths vs 255 deaths (RR = 0.98, 95% CI = 0.79–1.22; P = .86). By the end of follow-up, there was no significant difference between groups in breast cancer deaths (209 vs 474, RR = 0.88, 95% CI = 0.74–1.03; P = .13).

Per protocol analysis of the effect of being screened in the intervention period, adjusted for selection bias, showed a significant reduction in mortality in the intervention group at 10 years (RR = 0.66, 95% CI = 0.46–0.95; P = .025), but no significant reduction after more than 10 years of follow-up (RR = 0.98, 95% CI = 0.75–1.27; P = .89) and no significant reduction overall (RR = 0.84, 95% CI = 0.68–1.04; P = .11).

In a post hoc analysis including cancers diagnosed in the period up to and including the first NHSBSP screening, there was a significant reduction in mortality in the intervention group at 10 years (83 vs 219 deaths, RR = 0.75, 95% CI = 0.58–0.97; P = .029), no significant reduction after more than 10 years of follow-up (133 vs 279 deaths, RR = 0.95, 95% CI = 0.77–1.17; P = .63), and no significant difference overall (216 vs 498 deaths, RR = 0.86, 95% CI = 0.73–1.01; P = .068).

The absolute difference in breast cancer mortality between groups was –0.6 deaths per 1,000 women invited for screening, with this reduction being relatively stable over time throughout the study period. This figure implies that 1,667 women in the 40- to 49-year age group would need to be invited for screening and 1,150 would need to be screened (based on the 69% average participation rate) to prevent one breast cancer death in this age group.

A post hoc analysis showed that years of life lost due to breast cancer mortality were 67.4/1,000 women in the intervention group vs 78.9 years/1,000 women in the control group. This is equivalent to 11.5 years saved per 1,000 women invited to screening in the intervention group (P = .031) and a total of 620 years of life saved.

Incidence of Breast Cancer

Up to immediately before first NHSBSP screening, the incidence of breast cancer was significantly higher in the intervention group (953 vs 1,731, RR = 1.09; P = .047). No significant differences were found for the period up to and including the first NHSBSP screening (1,125 vs 2,247, RR = 0.99; P = .79) or at the end of follow-up (2,617 vs 5,260, RR = 0.99; P = .70).

Overall Mortality

Among all participants, no significant differences between groups were observed for all-cause mortality by the end of follow-up (RR = 1.01, P = .66), mortality from causes other than breast cancer (RR = 1.02, P = .43), death from all cancers (RR = 0.99, P = .74), or deaths from ischemic heart disease (RR = 1.03, P = .72).

Among women with breast cancer, there was a significant reduction in death from any cause in the intervention group (RR = 0.87, P = .024) and a nonsignificant reduction in death from all causes except breast cancer (RR = 0.86, P = .24).

The investigators concluded: “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.” 

DISCLOSURE: The study was funded by the National Institute for Health Research Health Technology Assessment program. Dr. Duffy has received research grants from the National Institute for Health Research, in addition to that for this trial.

REFERENCE

1. Duffy SW, Vulkan D, Cuckle H, et al: Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age Trial): Final results of a randomised, controlled trial. Lancet Oncol 21:1165-1172, 2020.