Mammography screening: A major issue in medicine
Mammography screening: A major issue in medicine
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DOI：
10.1016/j.ejca.2017.11.002
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发表时间：
2018-02-01
影响因子：
8.4
通讯作者：
Boniol, Mathieu
中科院分区：
文献类型：
--
作者：
Autier, Philippe;Boniol, Mathieu
在大多数高收入国家，乳腺癌死亡率正在下降。乳房x光检查在这些下降中所起的作用备受争议。筛查通过降低预后不良的晚期癌症发病率影响癌症死亡率，而治疗和患者管理通过降低癌症病死率影响癌症死亡率。癌症筛查的有效性是一种筛查方法在人群中抑制晚期癌症发病率的能力。评估癌症筛查效果的方法是基于监测晚期癌症的年龄调整发病率，该发病率在筛查引入后应该会下降。同样，在进行筛查的地区，癌症特异性死亡率的下降速度应该比没有或筛查水平较低但患者管理相似的地区更快。这两个标准提供的证据表明，筛查结直肠癌和宫颈癌有助于降低与这两种癌症相关的死亡率。相比之下，儿童神经母细胞瘤筛查在21世纪初停止，因为这两个标准不符合。此外，过度诊断——即发现在受试者一生中不会危及生命的未进展的隐匿性神经母细胞瘤——是筛查的一个主要不良后果。越来越多的流行病学数据显示，在乳房x线摄影筛查已长期普及的人群中，晚期癌症的发病率没有或只有轻微下降，包括诊断时的新发转移性（IV期）癌症的发病率。此外，乳腺癌死亡率的降低在早期采用和高普及筛查的地区与在较晚采用和低普及筛查的地区是相似的。过度诊断很常见，在接受筛查的妇女中占所有乳腺癌的20%或更多，在筛查发现的癌症中占30-50%。过度诊断导致过度治疗，并对许多妇女造成相当大的身体、心理和经济伤害。过度诊断也对以百分比（而不是比率）或总生存率（而不是死亡率或特定阶段生存率）表示的临床结果的解释产生了相当大的破坏性影响。在采用筛检后，根治性乳房切除术的比率并没有下降，在一些国家（例如美利坚合众国）还在上升。因此，乳房x线摄影筛查的流行病学情况与神经母细胞瘤筛查非常相似。对瑞典乳房x光检查试验的重新评估表明，这些试验的设计和统计分析不同于所有筛查乳腺癌以外癌症的试验。我们发现令人信服的迹象表明，这些试验高估了与筛查相关的乳腺癌死亡率的降低，部分原因是统计分析本身，部分原因是治疗方法的改进和乳腺癌作为筛查组死亡的潜在原因的低报。在这方面，瑞典的试验应分别公布筛查组和对照组的特定阶段乳腺癌死亡率。大纽约健康保险计划试验的结果是有偏见的，因为未参加筛查的妇女中发生的乳腺癌病例和死亡少报。经过17年的随访，英国年龄试验显示，从39-41岁开始进行乳房x光检查没有任何好处。直到2005年左右，大多数乳房筛查的支持者都支持监测晚期癌症发病率的变化，并对乳腺癌死亡率进行比较研究，以评估乳房筛查的有效性。然而，为了缓解乳房x线摄影试验结果与人口数据之间的矛盾，乳房筛查的支持者选择改变评估癌症筛查有效性的标准，优先考虑基于发病率的死亡率（IBM）和病例对照研究。但实际上，IBM所有关于乳房x光检查的研究在设计中都有很强的生态成分。IBM在挪威进行的两项研究满足了所有方法学要求，但并没有记录与乳房x光检查相关的乳腺癌死亡率显著降低。由于他们倾向于夸大筛查的健康益处，病例对照研究可能表明，乳房x光检查可以降低乳腺癌以外疾病的死亡风险。已经进行了许多统计模型方法来估计筛查和患者管理对降低乳腺癌死亡率的贡献。运行这些模型需要未经验证的假设。例如，许多模型假设，如果没有进行筛查，大多数筛查检测到的无症状癌症将发展为有症状的晚期癌症。这一假设没有证据依据，因为很大一部分筛查检测到的乳腺癌是过度诊断，因此是非进展性肿瘤。在经过良好筛选的人群中，人口数据的积累降低了模型方法的相关性。不同筛查方式（如乳房x线照相术、数字乳房x线照相术、超声检查、磁共振成像（MRI）、三维断层合成（TDT））的性能比较集中在检出率上，即一种技术比其他技术检测出更多癌症的能力。然而，更高的检出率并不能说明预防间隔期和晚期癌症的能力，而可能只是反映了额外的过度诊断。在销售新的乳房成像技术之前，应该进行基于晚期癌症发病率和过度诊断评估的研究。乳腺癌高风险妇女（即30%以上的终生风险），如BRCA1/2突变妇女，需要密切监测乳房。MRI是首选的成像方法，直到最终采用更彻底的降低风险的选择。对于乳腺癌中度风险的妇女（即10-29%的终生风险），包括乳房x光检查显示乳腺密度极高的妇女，没有证据表明更频繁的乳房x光检查或其他方式的筛查实际上降低了乳腺癌死亡的风险。大量的流行病学数据表明，自1985年以来，在乳腺癌患者管理方面取得的进展已导致特定阶段的乳腺癌死亡率显著降低，即使是诊断时患有弥散性疾病（即第四阶段癌症）的患者也是如此。相反，流行病学数据表明乳房x光检查对乳腺癌死亡率下降的贡献很小。此外，治疗越有效，乳房x光筛查的利弊平衡就越不利。需要新的、有效的乳房筛查方法，以及基于风险的筛查策略研究。(C) 2017 Elsevier Ltd.版权所有。
Breast cancer mortality is declining in most high-income countries. The role of mammography screening in these declines is much debated.Screening impacts cancer mortality through decreasing the incidence of number of advanced cancers with poor prognosis, while therapies and patient management impact cancer mortality through decreasing the fatality of cancers. The effectiveness of cancer screening is the ability of a screening method to curb the incidence of advanced cancers in populations. Methods for evaluating cancer screening effectiveness are based on the monitoring of age-adjusted incidence rates of advanced cancers that should decrease after the introduction of screening. Like-wise, cancer-specific mortality rates should decline more rapidly in areas with screening than in areas without or with lower levels of screening but where patient management is similar. These two criteria have provided evidence that screening for colorectal and cervical cancer contributes to decreasing the mortality associated with these two cancers. In contrast, screening for neuroblastoma in children was discontinued in the early 2000s because these two criteria were not met. In addition, overdiagnosis - i.e. the detection of non-progressing occult neuroblastoma that would not have been life-threatening during the subject's lifetime - is a major undesirable consequence of screening.Accumulating epidemiological data show that in populations where mammography screening has been widespread for a long time, there has been no or only a modest decline in the incidence of advanced cancers, including that of de novo metastatic (stage IV) cancers at diagnosis. Moreover, breast cancer mortality reductions are similar in areas with early introduction and high penetration of screening and in areas with late introduction and low penetration of screening. Overdiagnosis is commonplace, representing 20% or more of all breast cancers among women invited to screening and 30-50% of screen-detected cancers. Overdiagnosis leads to overtreatment and inflicts considerable physical, psychological and economic harm on many women. Overdiagnosis has also exerted considerable disruptive effects on the interpretation of clinical outcomes expressed in percentages (instead of rates) or as overall survival (instead of mortality rates or stage-specific survival). Rates of radical mastectomies have not decreased following the introduction of screening and keep rising in some countries (e.g. the United States of America (USA)). Hence, the epidemiological picture of mammography screening closely resembles that of screening for neuroblastoma.Reappraisals of Swedish mammography trials demonstrate that the design and statistical analysis of these trials were different from those of all trials on screening for cancers other than breast cancer. We found compelling indications that these trials overestimated reductions in breast cancer mortality associated with screening, in part because of the statistical analyses themselves, in part because of improved therapies and underreporting of breast cancer as the underlying cause of death in screening groups. In this regard, Swedish trials should publish the stage-specific breast cancer mortality rates for the screening and control groups separately. Results of the Greater New York Health Insurance Plan trial are biased because of the underreporting of breast cancer cases and deaths that occurred in women who did not participate in screening. After 17 years of follow-up, the United Kingdom (UK) Age Trial showed no benefit from mammography screening starting at age 39-41.Until around 2005, most proponents of breast screening backed the monitoring of changes in advanced cancer incidence and comparative studies on breast cancer mortality for the evaluation of breast screening effectiveness. However, in an attempt to mitigate the contradictions between results of mammography trials and population data, breast-screening proponents have elected to change the criteria for the evaluation of cancer screening effectiveness, giving precedence to incidence-based mortality (IBM) and case-control studies. But practically all IBM studies on mammography screening have a strong ecological component in their design. The two IBM studies done in Norway that meet all methodological requirements do not document significant reductions in breast cancer mortality associated with mammography screening. Because of their propensity to exaggerate the health benefits of screening, case-control studies may demonstrate that mammography screening could reduce the risk of death from diseases other than breast cancer.Numerous statistical model approaches have been conducted for estimating the contributions of screening and of patient management to reductions in breast cancer mortality. Unverified assumptions are needed for running these models. For instance, many models assume that if screening had not occurred, the majority of screen-detected asymptomatic cancers would have progressed to symptomatic advanced cancers. This assumption is not grounded in evidence because a large proportion of screen-detected breast cancers represent overdiagnosis and hence non-progressing tumours. The accumulation of population data in well-screened populations diminishes the relevance of model approaches.The comparison of the performance of different screening modalities - e.g. mammography, digital mammography, ultrasonography, magnetic resonance imaging (MRI), three-dimensional tomosynthesis (TDT) - concentrates on detection rates, which is the ability of a technique to detect more cancers than other techniques. However, a greater detection rate tells little about the capacity to prevent interval and advanced cancers and could just reflect additional overdiagnosis. Studies based on the incidence of advanced cancers and on the evaluation of overdiagnosis should be conducted before marketing new breast-imaging technologies.Women at high risk of breast cancer (i.e. 30% lifetime risk and more), such as women with BRCA1/2 mutations, require a close breast surveillance. MRI is the preferred imaging method until more radical risk-reduction options are eventually adopted. For women with an intermediate risk of breast cancer (i.e. 10-29% lifetime risk), including women with extremely dense breast at mammography, there is no evidence that more frequent mammography screening or screening with other modalities actually reduces the risk of breast cancer death.A plethora of epidemiological data shows that, since 1985, progress in the management of breast cancer patients has led to marked reductions in stage-specific breast cancer mortality, even for patients with disseminated disease (i.e. stage IV cancer) at diagnosis. In contrast, the epidemiological data point to a marginal contribution of mammography screening in the decline in breast cancer mortality. Moreover, the more effective the treatments, the less favourable are the harm-benefit balance of screening mammography.New, effective methods for breast screening are needed, as well as research on risk-based screening strategies. (C) 2017 Elsevier Ltd. All rights reserved.