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: Evidence was needed to determine the optimum frequency of mammographic surveillance for women after diagnosis of breast cancer due to variation in practice globally.

Methods: Multicentre, randomised, phase III trial of annual versus less frequent mammography (2-yearly after conservation surgery; 3-yearly after a mastectomy) for women aged 50 years or over at initial diagnosis of invasive or non-invasive breast cancer and were recurrence free 3-years post curative surgery. Participants were randomised 3 years post curative surgery and followed up on study for 6 years.
Primary outcome was breast-cancer-specific-survival (BCSS). Secondary outcomes included recurrence-free-interval (RFI) and overall-survival (OS). 5000 women provided 85% power to detect a 3% absolute non-inferiority (NI) margin for BCSS with 2.5% one-sided alpha. This trial is registered as an International Standardised Randomised Controlled Trial (ISRCTN48534559).

Findings: 5235 women were randomised between April 2014 and September 2018, from 114 UK sites. 3858 (74%) women were aged 60 years or over, 4202 (80%) had undergone conservation surgery, 4576 (87%) had invasive disease, 1159 (22%) had node positive disease, 4330 (83%) had ER positive tumours. With median 5.7 years follow-up (8.7 years post-curative-surgery), 343 women have died; 116 of breast cancer (61 on annual arm; 55 on less frequent arm). Five-year BCSS was 98.1% (95% CI 97.5-98.6%) for annual arm and 98.3% (95% CI 97.8-98.8%) for less frequent arm; hazard ratio (HR) 0.92 (95% CI 0.64-1.32) demonstrated NI of less frequent mammograms at the 1% margin (NI p=0.003). Five-year RFI was 94.1% (95% CI 93.1-94.9%) and OS was 94.7% (95% CI 93.8-95.5%) for the annual arm and 94.5% (95% CI 93.5-95.3%) and 94.5% (95% CI 93.5-95.3%), respectively, for the less frequent arm. NI was demonstrated at the 2% margin for both RFI (HR 1.00 (95% CI 0.81-1.23); NI p=0.006) and OS (HR 1.07 (95% CI 0.87 -1.33); NI p=0.008).
Interpretation: For patients aged 50 years or older and 3-years post diagnosis, less frequent mammograms were non-inferior compared to annual mammograms and should be considered for this population.