medwireNews: Extending mammography screening to include women in their 40s may reduce breast cancer mortality rates compared with a later screening induction without increasing the risk for overdiagnosis, the UK Age trial investigators report.
“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,” report Stephen Duffy, from Queen Mary University of London in the UK, and co-authors in The Lancet Oncology.
The study, performed at 23 UK screening units, included 53,883 women aged 39–41 years old, who were invited to undergo annual mammography up to and including the age of 48 years and followed up for a median 22.8 years.
Their findings were compared with screening results for 106,953 women who received a regular invitation to the National Health Service Breast Screening Programme (NHSBSP) when they were around age 50 years, and acted as study controls.
There was a significant decrease in breast cancer mortality risk in the early screening group at 10 years of follow-up compared with the control group, with 83 versus 219 deaths and a significant relative rate (RR) of 0.75.
However, there was no further decrease in breast cancer mortality risk after this time in the early screening group versus controls, with 209 versus 474 deaths by the end of follow-up and a nonsignificant RR of 0.88.
The absolute difference in breast cancer mortality risk was –0.6 deaths per 1000 women invited for early screening, the investigators say. When considering a 69% average participating rate, 1667 women would have to be invited and 1150 women screened at age 40–49 years to prevent one breast cancer death.
Post-hoc analysis suggested the early screening intervention provided an additional 11.5 years per 1000 women invited, translating to 620 life–years saved.
The team reports that the cumulative incidence of total cancers up to the time of the first NHSBSP screen were 953 cases in the intervention group and 1731 among controls, a significant difference (RR=1.09), but by the end of follow-up, there were a comparable 2617 versus 5260 cancers, respectively.
There were no differences in the groups with regard to the incidence of invasive breast cancer; while in situ tumors were more common during the initial intervention period than among controls, this difference disappeared by the end of follow-up.
The authors suggest these findings indicate “at worst modest overdiagnosis in this age group, and that any overdiagnosed cancers would otherwise be diagnosed at NHSBSP screening from age 50 years onwards.”
But they admit that they “cannot directly observe or estimate overdiagnosis in a trial in which the controls group also receives screening, albeit later than the intervention group.”
The author of an accompanying comment finds the conclusion of no overdiagnosis in either group as “surprising” and suggests that as this risk increases with age, “it is possible that overdiagnosis occurred in both groups after the age of 50 years, but could not be detected because of the design of the trial.”
Moreover, Anthony Miller, from the University of Toronto in Ontario, Canada, believes that “the debate over whether to initiate breast screening at age 40 or 50 years will not have been resolved by the UK Age trial, as the lack of a control group who were not offered screening at any age precluded determining whether either group in the trial derived any benefit.”
He concludes: “Those who favour screening will be left with a conundrum, but those who believe that mammography screening has little or no benefit will feel their views have been justified.”
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Lancet Oncol 2020; doi:10.1016/S1470-2045(20)30398-3
Lancet Oncol 2020; doi:10.1016/S1470-2045(20)30428-9