Ann. Intern. Med：乳房X线筛查或与过度诊断性乳腺癌有关

4月3日，《内科学年鉴》（Annals of Internal Medicine）杂志发表的一项研究结果表明，乳房X线筛查可能与15%~25%的“过度诊断性”乳腺癌有关。哈佛公共卫生学院的Mette Kalager博士介绍，这与既往其他国家的研究结果一致，后者报告的估计过度诊断率为0%~54%不等，随机对照试验报告的过度诊断率约为30%。

这项挪威研究的结果进一步表明，对非致死性癌症的过度诊断和不必要的治疗，会带来不容忽视的伦理和临床问题，而且会使人怀疑是否有必要继续开展乳房X线筛查。

自从1996年开展政府资助的乳房X线筛查项目以来，这一筛查在挪威逐渐变得常见，但各地的推广进程并不一致，经过10年时间才实现了普遍推广。自2005年以后，挪威所有50~69岁女性均被建议每2年筛查1次，其中约77%依从了这一建议。“推广进程的不一致为研究者提供了机会，得以比较开展和未开展筛查的地区的乳腺癌发病率和过度诊断情况，并且使研究者可以用两种方法进行评估。”

该研究中的过度诊断是指，假如不接受筛查一生中都不会出现临床症状的乳腺癌。即乳腺癌永远不会进展为临床期，或者在乳腺癌出现临床表现之前患者已死于其他原因，因此这类患者获得诊断和治疗不会带来任何生存益处。

该研究的对象包括39,888例在1996~2005年期间被诊断为侵袭性乳腺癌的女性，其中27,238例诊断时年龄为50~79岁。共有7,793例在开始常规筛查后获得诊断。

采用第一种估计方法的完全校正分析显示，在乳房X线筛查中发现的乳腺癌病例中有15%~20%——即1,169~1,948例——属于过度诊断。采用第二种估计方法进行分析，18%~25%的病例为过度诊断。因此，总体过度诊断率为15%~25%。

而且，进展期乳腺癌的比例随着时间推移而逐渐下降，筛查组与未筛查组降至同一水平，而Ⅰ期乳腺癌的比例仅在筛查组女性中显著增加。这一结果提示，乳房X线筛查发现的乳腺癌几乎均为早期、低危肿瘤。“我们的结果提示，晚期癌症较少可能是患者更加警惕的结果，而不是筛查本身的功劳。”

华盛顿大学的Joann G. Elmore博士和哈佛医学院的Suzanne W. Fletcher博士在随刊述评中指出：“没必要太纠结于过度诊断的确切范围，当务之急是意识到任何程度的过度诊断都是严重的，必须尽快解决这一问题。”一种减少过度诊断的方法是，调整乳房X线检查结果的“异常”阈值。同时，对于确定的病变可以建议继续严密观察而不必立即活检(Ann. Intern. Med. 2012;156:536-7)。“我们有义务告知女性这种过度诊断现象，而实际上多数患者教育都没有提及这一问题。”

Elmore博士在非营利性医疗决策告知基金会出版的患者教育材料中担任了医学编辑，Fletcher博士报告称从事乳腺癌筛查达36年之久，并在1980年代早期为美国预防服务工作组提供了服务。这项研究获得了挪威前沿科学研究理事会的支持。Kalager博士及其合著者无利益冲突披露。（生物谷Bioon.com）

Doi:
PMC:
PMID:22473436

Overdiagnosis of Invasive Breast Cancer Due to Mammography Screening: Results From the Norwegian Screening Program

Mette Kalager, MD; Hans-Olov Adami, MD, PhD; Michael Bretthauer, MD, PhD; and Rulla M. Tamimi, ScD

Background: Precise quantification of overdiagnosis of breast cancer (defined as the percentage of cases of cancer that would not have become clinically apparent in a woman's lifetime without screening) due to mammography screening has been hampered by lack of valid comparison groups that identify incidence trends attributable to screening versus those due to temporal trends in incidence.

Objective: To estimate the percentage of overdiagnosis of breast cancer attributable to mammography screening.

Design: Comparison of invasive breast cancer incidence with and without screening.

Setting: A nationwide mammography screening program in Norway (inviting women aged 50 to 69 years), gradually implemented from 1996 to 2005.

Participants: The Norwegian female population.

Measurements: Concomitant incidence of invasive breast cancer from 1996 to 2005 in counties where the screening program was implemented compared with that in counties where the program was not yet implemented. To adjust for changes in temporal trends in breast cancer incidence, incidence rates during the preceding decade were also examined. The percentage of overdiagnosis was calculated by accounting for the expected decrease in incidence following cessation of screening after age 69 years (approach 1) and by comparing incidence in the current screening group with incidence among women 2 and 5 years older in the historical screening groups, accounting for average lead time (approach 2).

Results: A total of 39 888 patients with invasive breast cancer were included, 7793 of whom were diagnosed after the screening program started. The estimated rate of overdiagnosis attributable to the program was 18% to 25% (P < 0.001) for approach 1 and 15% to 20% (P < 0.001) for approach 2. Thus, 15% to 25% of cases of cancer are overdiagnosed, translating to 6 to 10 women overdiagnosed for every 2500 women invited.