乳腺癌筛查是否仍然需要东方神手？
乳腺钼靶已被西方国家广泛用于乳腺癌筛查，逐步取代了触诊等临床乳房体检。不过，由于乳腺钼靶的成本和复杂性，可能并不适用于中低收入国家。此外，中低收入国家大多数乳腺癌发病年龄都小于50岁，该年龄段女性乳腺密度较高，乳腺钼靶效果较差。
2021年2月24日，国际四大医学期刊之一、英国医学会《英国医学杂志》正刊发表印度孟买国立霍米巴哈学院塔塔纪念中心的研究报告，探讨了临床乳房体检筛查能否降低20年后乳腺癌诊断时分期和乳腺癌所致死亡率。
NCT00632047 (CTRI/2010/091/001205): Early Detection of Breast Cancer and Cervical Cancer in Women in India
该大样本前瞻群组随机对照研究将印度孟买20个不同地理区域随机分为10个筛查地区和10个对照地区，从1998年5月开始，入组35～64岁无乳腺癌史女性15万1538例：
筛查地区女性7万5360例，每2年由经过培训的女性初级卫生保健工作者进行临床乳房体检筛查和癌症宣传教育，共计4轮；随后每2年进行上门家访主动监测，共计5轮。
对照地区女性7万6178例，首先进行癌症宣传教育；随后每2年进行上门家访主动监测，共计8轮。
主要结局衡量指标：乳腺癌诊断时分期降低，乳腺癌所致死亡率降低。
结果，截至2019年3月，筛查地区与对照地区相比：
乳腺癌检出年龄显著较早：55.18±9.10比56.50±9.10岁（P=0.01）
晚期乳腺癌比例显著较低：37%比47%（220比271例，P=0.001）
乳腺癌所致死亡比例较低：10万分之20.82比24.62（低15%，95%置信区间：18.25～23.97、21.71～28.04；比值比：0.85，95%置信区间：0.71～1.01，P=0.07）
不过，事后亚组分析表明，筛查地区与对照地区相比：
年龄≥50岁女性：乳腺癌所致死亡比例低29%（10万分之24.62比34.68，95%置信区间：20.62～29.76、27.54～44.37；比值比：0.71，95%置信区间：0.54～0.94，P=0.02）
年龄<50岁女性：乳腺癌所致死亡比例低7%（10万分之19.53比21.03，95%置信区间：17.24～22.29、18.97～23.44；比值比：0.93，95%置信区间：0.79～1.09，P=0.37）
筛查地区与对照地区相比，任何原因所致死亡比例低5%（比值比：0.95，95%置信区间：0.81～1.10，P=0.49）。
因此，该研究结果表明，每两年进行临床乳房体检筛查可显著降低乳腺癌诊断时分期，乳腺癌所致死亡比例降低不显著。不过，年龄≥50岁女性乳腺癌所致死亡比例显著降低29%，年龄<50岁女性乳腺癌所致死亡比例降低不显著。对于中低收入国家，临床乳房体检应被考虑用于乳腺癌筛查。
BMJ. 2021 Feb 24;372:n256.
Effect of screening by clinical breast examination on breast cancer incidence and mortality after 20 years: prospective, cluster randomised controlled trial in Mumbai.
Indraneel Mittra, Gauravi A Mishra, Rajesh P Dikshit, Subhadra Gupta, Vasundhara Y Kulkarni, Heena Kauser A Shaikh, Surendra S Shastri, Rohini Hawaldar, Sudeep Gupta, C S Pramesh, Rajendra A Badwe.
Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India.
OBJECTIVE: To test the efficacy of screening by clinical breast examination in downstaging breast cancer at diagnosis and in reducing mortality from the disease, when compared with no screening.
DESIGN: Prospective, cluster randomised controlled trial.
SETTING: 20 geographically distinct clusters located in Mumbai, India, randomly allocated to 10 screening and 10 control clusters; total trial duration was 20 years (recruitment began in May 1998; database locked in March 2019 for analysis).
PARTICIPANTS: 151538 women aged 35-64 with no history of breast cancer.
INTERVENTIONS: Women in the screening arm (n=75360) received four screening rounds of clinical breast examination (conducted by trained female primary health workers) and cancer awareness every two years, followed by five rounds of active surveillance every two years. Women in the control arm (n=76178) received one round of cancer awareness followed by eight rounds of active surveillance every two years.
MAIN OUTCOME MEASURES: Downstaging of breast cancer at diagnosis and reduction in mortality from breast cancer.
RESULTS: Breast cancer was detected at an earlier age in the screening group than in the control group (age 55.18 (standard deviation 9.10) v 56.50 (9.10); P=0.01), with a significant reduction in the proportion of women with stage III or IV disease (37% (n=220) v 47% (n=271), P=0.001). A non-significant 15% reduction in breast cancer mortality was observed in the screening arm versus control arm in the overall study population (age 35-64; 20.82 deaths per 100000 person years (95% confidence interval 18.25 to 23.97) v 24.62 (21.71 to 28.04); rate ratio 0.85 (95% confidence interval 0.71 to 1.01); P=0.07). However, a post hoc subset analysis showed nearly 30% relative reduction in breast cancer mortality in women aged 50 and older (24.62 (20.62 to 29.76) v 34.68 (27.54 to 44.37); 0.71 (0.54 to 0.94); P=0.02), but no significant reduction in women younger than 50 (19.53 (17.24 to 22.29) v 21.03 (18.97 to 23.44); 0.93 (0.79 to 1.09); P=0.37). A 5% reduction in all cause mortality was seen in the screening arm versus the control arm, but it was not statistically significant (rate ratio 0.95 (95% confidence interval 0.81 to 1.10); P=0.49).
CONCLUSIONS: These results indicate that clinical breast examination conducted every two years by primary health workers significantly downstaged breast cancer at diagnosis and led to a non-significant 15% reduction in breast cancer mortality overall (but a significant reduction of nearly 30%in mortality in women aged ≥50). No significant reduction in mortality was seen in women younger than 50 years. Clinical breast examination should be considered for breast cancer screening in low and middle income countries.
TRIAL REGISTRATION: CTRI/2010/091/001205; ClinicalTrials.gov NCT00632047
DOI: 10.1136/bmj.n256