The results of a multicentre, randomised, phase III Mammo-50 study conducted in the UK demonstrate non-inferiority of less frequent mammograms compared with annual mammographic surveillance among women aged 50 years or older at initial diagnosis of breast cancer who are recurrence-free at 3 years post diagnosis.
The findings could have a large impact globally because many women are currently offered annual mammograms indefinitely, which puts a burden both on healthcare systems and on the patients, in terms of increased radiation exposure, raised anxiety, and higher out-of-pocket costs according to Prof. Janet A Dunn of the Warwick Clinical Trials Unit, University of Warwick in Coventry, UK and colleagues, who published the findings on 1 February 2025 in The Lancet.
The authors wrote in the background that mammographic surveillance helps detect new primary breast cancers or recurrence. The early detection of local recurrence is associated with improved survival. Survival is better when local recurrence is found by mammography instead of physical examination and in patients who are asymptomatic compared with those who are symptomatic.
Locoregional recurrences have become less common in recent years suggesting that modern surgical practice and systemic therapy have been effective in preventing local recurrence. One of the strongest predictors of local recurrence is young age. Women aged 50 years or younger have poorer outcomes when local recurrence occurs compared with women older than 50 years.
The reduction in local recurrence rates over the past decade, the low recurrence rate, and the prolonged lead time of screening in older women raise the possibility of safe de-escalation of mammographic surveillance in this patient population.
The aim of the Mammo-50 study was to ascertain whether less frequent mammography is non-inferior in terms of breast cancer-specific survival in women aged 50 years or older at diagnosis, who are 3 years post treatment for operable breast cancer, and are disease-free. It was a multicentre, randomised, phase III study of annual mammography versus 2-yearly after conservation surgery or 3-yearly after a mastectomy for women aged 50 years or older at initial diagnosis of invasive or non-invasive breast cancer and who were recurrence-free 3 years post curative surgery.
The study was conducted at 114 National Health Service hospitals in the UK. Participants were randomly assigned 1:1 to annual or less frequent mammograms at 3 years post curative surgery and were followed up for 6 years. The co-primary outcomes were breast cancer-specific survival and cost-effectiveness. The cost-effectiveness analysis will be reported elsewhere.
Breast cancer-specific survival was assessed in the intention-to-treat population. Secondary outcomes were recurrence-free interval, overall survival, and referrals back to the hospital system. A total 5000 women provided 90% power to detect a 3% absolute non-inferiority margin for breast cancer-specific survival with 2.5% one-sided significance. Recruitment is complete, but longer-term follow-up is ongoing.
Between 22 April 2014 and 28 September 2018, 2618 women were randomly assigned to annual mammography and 2617 to less frequent mammography; 3858 women (73.6%) were aged 60 years or older, 4202 (80.3%) had undergone conservation surgery, 4576 (87.4%) had invasive disease, 1159 (22.1%) had node-positive disease, and 4330 (82.7%) had oestrogen receptor-positive tumours.
With a median of 5.7 years follow-up (interquartile range 5.0–6.0; 8.7 years post curative surgery), 343 women died, including 116 who died of breast cancer (61 in the annual mammography group and 55 in the less frequent mammography group).
5-year breast cancer-specific survival was 98.1% (95% confidence interval [CI] 97.5–98.6) in the annual mammography group and 98.3% (95% CI 97.8–98.8) in the less frequent mammography group (hazard ratio 0.92, 95% CI 0.64–1.32), demonstrating non-inferiority of less frequent mammography at the pre-specified 3% margin (non-inferiority p < 0.0001).
5-year recurrence-free interval was 94.1% (95% CI 93.1–94.9) in the annual mammography group and 94.5% (93.5–95.3) in the less frequent mammography group. Overall survival at 5 years was 94.7% (95% CI 93.8-95.5%) and 94.5% (95% CI 93.5–95.3), respectively. In total, 224 of 345 breast cancer events (64.9%) were detected from emergency admissions or symptomatic referrals back to the hospital system, including 108 of 175 (61.7%) in the annual mammography group and 116 of 170 (68.2%) in the less frequent mammography group.
The authors concluded that the study shows that women aged 50 years or older at diagnosis of breast cancer who have undergone annual mammographic surveillance for 3 years post diagnosis, and at which time show no signs of recurrence, can safely have less frequent mammograms. Women who have had a mastectomy should have mammography based on the lead time of screening in that age group; this would suggest 2-3 yearly mammography for women older than 50 years at diagnosis. For women post wide local incision for invasive cancer, after annual mammography up to 3 years to establish baseline appearances, they could safely have less frequent mammography from then on. Mammo-50 provides the evidence to change guidelines, both within the UK and internationally.
In an accompanied comment, Dr. Ritse M Mann of the Department of Medical Imaging, Radboud University Medical Center in Nijmegen and Department of Radiology, Netherlands Cancer Institute in Amsterdam, Netherlands wrote that a randomised controlled study on surveillance mammography such as this is unique and the efforts of the investigators must be applauded. Current guidelines advocate for policies that are, at best, based on expert consensus and retrospective cohort studies. This study in essence shows that regular screening in low-risk women might prevent negative consequences of a second cancer similarly to long-term hospital-based surveillance.
The study was funded by the UK National Institute for Health Research Health Technology Assessment programme.
References
- Dunn JA, Donnelly P, Elbeltagi N, et al. Annual versus less frequent mammographic surveillance in people with breast cancer aged 50 years and older in the UK (Mammo-50): a multicentre, randomised, phase 3, non-inferiority trial. The Lancet 2025;405(10476):396–407.
- Mann RM. Rethinking surveillance after breast cancer. The Lancet 2025;405(10476):356-358.