Dunn Janet A, Donnelly Peter, Elbeltagi Nada, Marshall Andrea, Hopkins Amy, Thompson Alastair M, Audisio Riccardo, Pinder Sarah E, Cameron David A, Hartup Sue, Turner Lesley, Young Annie, Higgins Helen, Watson Eila K, Gasson Sophie, Barrett-Lee Peter J, Hulme Claire, Shinkins Bethany, Hall Peter S, Evans Andrew
Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.
Torbay and South Devon NHS Foundation Trust, Torquay, UK.
Lancet. 2025 Feb 1;405(10476):396-407. doi: 10.1016/S0140-6736(24)02715-6.
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.
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.
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.
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.
National Institute for Health Research Health Technology Assessment programme.
乳腺癌确诊后女性乳腺钼靶检查的频率在全球范围内各不相同。本研究的目的是评估对于50岁及以上女性，低于每年一次的乳腺钼靶检查在乳腺癌特异性生存方面是否不劣于每年检查。
Mammo-50是一项多中心、随机、3期试验，针对初次诊断为浸润性或非浸润性乳腺癌且在根治性手术后3年无复发的50岁及以上女性，比较每年进行乳腺钼靶检查与较低频率检查（保乳手术后每2年一次；乳房切除术后每3年一次）的效果。该试验在英国114家国民保健服务医院进行。参与者在根治性手术后3年被随机分配（1:1）接受每年或较低频率的乳腺钼靶检查，并随访6年进行。共同主要结局是乳腺癌特异性生存和成本效益。成本效益分析将在其他地方报告。在意向性分析人群中评估乳腺癌特异性生存。次要结局是无复发生存期、总生存以及返回医院系统的转诊情况。5000名女性提供了90%的检验效能，以检测乳腺癌特异性生存方面3%的绝对非劣效性界值，单侧显著性水平为2.5%。该试验在国际标准随机对照试验编号注册库（ISRCTN registry）注册，编号为ISRCTN ******；招募工作已完成，但仍在进行长期随访。
在至期间，5235名女性被随机分配接受每年一次乳腺钼靶检查（n = 2618）或较低频率检查（n = 2617）。3858名（73.6%）女性年龄在60岁及以上，4202名（80.3%）接受了保乳手术，4576名（87.4%）患有浸润性疾病，1159名（22.1%）有淋巴结阳性疾病，4330名（82.7%）患有雌激素受体阳性肿瘤。中位随访时间为5.7年（四分位间距5.0 - 6.0；根治性手术后8.7年），343名女性死亡，其中116名死于乳腺癌（每年一次乳腺钼靶检查组61名，较低频率检查组55名）。每年一次乳腺钼靶检查组5年乳腺癌特异性生存率为98.1%（95%置信区间97.5 - 98.6），较低频率检查组为98.3%（97.8 - 98.8）（风险比0.92，95%置信区间0.64 - 1.32），表明较低频率检查在预先设定的3%界值下不劣于每年检查（非劣效性p < 0.0001）。每年一次乳腺钼靶检查组5年无复发生存率为94.1%（95%置信区间93.1 - 94.9），较低频率检查组为94.5%（93.5 - 95.3）。5年总生存率分别为94.7%（95%置信区间93.8 - 95.5%）和94.5%（93.5 - 95.3）。345例乳腺癌事件中的224例（6******）通过急诊入院或有症状转诊返回医院系统检测到，其中每年一次乳腺钼靶检查组175例中的108例（6******），较低频率检查组170例中的116例（6******）。
对于50岁及以上且确诊后3年的患者，较低频率的乳腺钼靶检查在乳腺癌特异性生存、无复发生存期和总生存方面不劣于每年一次的检查，该人群应考虑采用。
英国国家卫生研究院卫生技术评估项目。
