Mammographic surveillance in breast cancer patients aged 50 years or older: a synopsis of the Mammo-50 RCT

Annual surveillance mammograms for an unspecified period, after treatment for early breast cancer, are widely practised in the United States of America and Europe. Current UK guidelines recommend annual mammograms for 5 years, then reverts to 3-yearly screening. The aim of this trial was to evaluate whether less than annual mammography was non-inferior in terms of breast cancer-specific survival and cost-effectiveness in women aged 50 years or older at diagnosis and 3 years post curative surgery.

We conducted a multicentre, randomised phase III trial of annual mammography versus less-frequent mammography (2-yearly after conservation surgery or 3-yearly after mastectomy). Women were eligible if aged ≥ 50 years at initial diagnosis of breast cancer (invasive or ductal carcinoma in situ) and recurrence-free 3 years post curative surgery. The trial was conducted at 114 NHS hospitals in the UK. Participants were randomly assigned (1 : 1) to annual or less-frequent mammograms; followed up for 6 years. Coprimary outcomes were breast cancer-specific-survival and cost-effectiveness; secondary outcomes included recurrence-free interval and overall survival. Analyses were by intention to treat, with a pre-planned per-protocol analysis. Planned sample size was 5000. Clinical results are now reported.

Five thousand two hundred and thirty-five women were randomised between April 2014 and September 2018. With a median of 5.7-year follow-up, 343 women have died, of whom 116 died of breast cancer (61 on annual arm; 55 on less-frequent arm). Breast cancer-specific-survival at 5 years was 98% on both arms with a hazard ratio of 0.92 (95% confidence interval 0.64 to 1.32), which demonstrated non-inferiority of less-frequent mammograms at the 3% margin (non-inferiority p < 0.0001) and the 1% margin (non-inferiority p = 0.003). Non-inferiority was demonstrated at the 2% level for both recurrence-free interval [hazard ratio 1.00 (95% confidence interval 0.83 to 1.28); non-inferiority p = 0.0024] and overall survival [hazard ratio 1.07 (95% confidence interval 0.87 to 1.33); non-inferiority p = 0.008]. Less-frequent mammograms were associated with a significant cost saving (mean difference £544, 95% confidence interval -£1116 to £26), heavily driven by mammogram costs. Incorporating societal costs resulted in a larger cost-saving (£1543 per person, 95% confidence interval -£2416 to -£669), increasing cost-effectiveness. There was no impact of less-frequent mammograms on patients' quality of life.

For patients aged ≥ 50 years and 3 years post diagnosis, less-frequent mammograms were non-inferior and cost-effective compared with annual mammograms, with no detriment to patients' quality of life. Mammo-50 provides evidence to inform guideline development.

Adherence to the mammographic schedules was 76%, though the per-protocol analysis showed no difference compared to the intention to treat results. The majority of the participants had small lower-grade oestrogen receptor-positive tumours and were from a White ethnic group.

More research is needed for women with ductal carcinoma in situ; women aged under 50 years old at diagnosis and different ethnic groups, especially those women of Black ethnicity who tend to present younger.

This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 11/25/03.