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.

BACKGROUND

The frequency of mammographic surveillance for women after diagnosis of breast cancer varies globally. The aim of this study was to evaluate whether less than annual mammography was non-inferior in terms of breast cancer-specific survival in women aged 50 years or older.

METHODS

Mammo-50 was a multicentre, randomised, phase 3 trial of annual versus less frequent mammography (2-yearly after conservation surgery; 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 trial 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. 5000 women provided 90% power to detect a 3% absolute non-inferiority margin for breast cancer-specific survival with 2·5% one-sided significance. The trial was registered with the ISRCTN registry, ISRCTN48534559; recruitment is complete but longer-term follow-up is ongoing.

FINDINGS

Between April 22, 2014, and Sept 28, 2018, 5235 women were randomly assigned to annual mammography (n=2618) or less frequent mammography (n=2617). 3858 (73·6%) women 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 (IQR 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% CI 97·5-98·6) in the annual mammography group and 98·3% (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% (93·5-95·3), respectively. 224 (64·9%) of 345 breast cancer events were detected from emergency admissions or symptomatic referrals back to the hospital system, including 108 (61·7%) of 175 in the annual mammography group and 116 (68·2%) of 170 in the less frequent mammography group.

INTERPRETATION

For patients aged 50 years or older and at 3 years post diagnosis, less frequent mammograms were non-inferior compared with annual mammograms for breast cancer-specific survival, recurrence-free interval, and overall survival, and should be considered for this population.

FUNDING

National Institute for Health Research Health Technology Assessment programme.