患者特征

与乳腺X线摄影准确性相关的女性特征包括:年龄、腺体密度、是否初次行乳腺X线摄影以及距离上次乳腺X线摄影的时间。使用乳腺X线摄影进行筛查时,较年轻女性相比于较老龄女性,其敏感性较低,假阳性率增高(更多信息参见 乳腺癌监管联合会中年龄对影像学结果的影响一节)。

对于任何年龄的女性而言,腺体密度较高均与敏感性下降有关,约下降10%到29%不等[1]。腺体密度高是一项遗传特性,通常表现为家族性特性;[2][3]但也会受到其他多种因素影响,包括年龄、内源性 [4]及外源性[5][6]激素[7]、选择性雌激素受体调节剂如他莫昔芬[8]、及饮食等[9]。激素疗法与腺体密度增高有关,其不仅与乳腺X线摄影敏感性下降相关,也与间期癌的发生率升高相关[10]

英国百万妇女研究发表的结果显示,对于50-64岁间的女性患者,以下三种患者特征与乳腺X线摄影筛查的敏感性及特异性降低相关,包括:绝经后激素替代治疗、既往乳腺手术史及体重指数小于25[11]。此外,距离最后一次乳腺筛查的时间间隔越长,再次行乳腺筛查检查的敏感性、召回率及肿瘤检出率均有所上升,同时特异性会下降[12]

为了提高乳腺X线摄影的敏感性,研究者提出以上方案:改变饮食习惯、根据月经周期行乳腺筛查、在检查前中止激素疗法、以及应用数字化X线成像仪器[13]。肥胖女性相比于低体重和正常体重的女性,乳腺X线摄影的敏感性相同,但假阳性率高了20%[14]

​肿瘤特征

某些肿瘤较其他类型相比更容易被乳腺X线摄影检出。此外,粘液性、小叶性及快速生长的肿瘤,由于在X线上的表现类似正常乳腺结构,可能会在筛查中被遗漏[15]。髓样癌出于同样的原因也可能会被漏诊[16]。而另外一些肿瘤,特别是伴有BRCA1/2突变的肿瘤,常常会表现为良性肿瘤特征[17][18]

医师特征

影像科医师的专业技能对于评价乳腺X线摄影的分析效能至关重要;而这种技能在不同的影像科医师间存在巨大而显著的差别。可能会影响放射科医师表现的因素包括:经验水平以及他们曾经阅读过的乳腺X线摄影片的数量[19]。敏感性和特异性之间往往存在一种折衷,比如较高的敏感性常常伴随较低的特异性。相比于社区医院的影像科医师,大型医疗中心的影像科医师在建议患者行进一步的活检检查时,其阳性预测值(PPV)往往更高[20]。乳腺影像方面的专科训练也可能会增加肿瘤的检出率,但是它同时也与较高的假阳性率有关[13]

机构特征

在控制患者特征及医师特征后,乳腺X线摄影能否能高效地筛查出肿瘤(特异性、PPV及曲线下面积[AUC])还取决于筛查机构,并与机构特征息息相关。较高检查准确性常常见于仅进行筛查的机构,这类机构需要满足以下几点:有专门的乳腺影像科医师、 单人阅片而非双人阅片、每年至少2次专业稽查[21]

不同机构在进行诊断性乳腺X线摄影时,其假阳性率相差巨大;对医疗事故顾虑较高的机构假阳性率通常会较高[22]。此外,为弱势群体的女性(少数民族或种族的女性、或低教育程度、低收入及乡村妇女)提供服务的机构相比于为非弱势群体的女性服务的机构,其假阳性率也会较高;这可能是因为该群体的女性患者对于进行进一步检查的依从性更差[23]。因此,如果一项研究没有对重要的患者特征进行调整,就有可能错误地高估准确性在机构间的差异[22]

​国家对比

对不同国家的乳腺X线摄影筛查进行对比研究显示,在筛查系统高度集中、存在国家质量保证项目的国家,筛查的特异性更高[24][25]。例如,一项研究发现美国的召回率是英国的2倍之多,而二者的肿瘤检出率并无差别。这样的对比可能受到社会、文化及经济等多种混杂因素的影响[25]

​初次筛查与随访筛查的对比及其筛查间隔

初次(第一次)行筛查检查发现乳腺癌的可能性最大。根据受检女性年龄不同,每1000例筛查女性中可检出9-26例乳腺癌。而随访筛查检出乳腺癌的可能性则有所下降,每1000例筛查女性中可检出1-3例乳腺癌[26]。如何确定两次乳腺X线摄影筛查之间的最佳间隔尚有争议。一般来说,用于研究乳腺癌相关死亡率的随机对照研究多采用固定的筛查间隔,且在不同临床试验间变异不大。英国一项前瞻性临床试验随机纳入年龄分布于50到62岁间女性患者,分为两组,分别以一年和三年为间隔进行规律的乳腺X线摄影筛查。尽管两组在检出肿瘤级别、淋巴结状态等方面基本相似,但在一年间隔组检出的多数肿瘤体积较小,且检出时间较三年组领先约7个月[27]

一项大型观察性研究发现,对于40岁的女性,如果每2年进行一次乳腺癌筛查,和每年一次筛查相比,在检出乳腺癌时肿瘤为晚期的风险轻度升高(分别为28%与21%;比值比(OR),1.35;95%置信区间[CI],1.01-1.81);在50岁或60岁的女性中进行类似对比,两组没有差别[28][29]

一项芬兰研究收录了年龄在40到49岁之间的14,765例女性,将这些女性分为两组:偶数年出生的女性每年进行一次筛查,奇数年出生的女性每三年进行一次筛查。但由于死亡病例数较小,无法判断两组的乳腺癌相关死亡率的差别。三年间隔组在100,738总人年数中有18例乳腺癌相关死亡病例;而1年间隔组在88,780总人年数中有18例乳腺癌相关死亡病例(风险比,0.88;95%CI。0.59-1.27)[30]

数字乳腺X线摄影

数字乳腺X线摄影的检查价格高于乳腺屏-片检查(SFM),但在数据储存及分享方面更为先进。不少临床试验比较了两种技术的筛查效果,得出的结论类似。

数字乳腺X线摄影筛查临床试验(DMIST)是一项大型队列研究,共纳入42,760例女性,分别在美国的33个研究中心进行乳腺数字或屏-片X线检查。结果提示两种成像技术在乳腺癌检出方面并无差别(数字成像术的AUC为0.78±0.02;屏-片成像术的AUC为0.74±0.02;P=0.18)。在年龄小于50岁的女性中,数字乳腺X线摄影对乳腺癌的检出更佳(数字成像术的AUC为0.84±0.03;屏-片成像术的AUC为0.69±0.05;P=0.002)。DMIST研究第二项分析结果显示,在年龄大于等于65岁的女性群体中,乳腺屏-片X线检查的肿瘤检出率更高(屏-片成像术的AUC为0.88;数字成像术的AUC为0.70;P=0.025);但上述结果在多重比较分析后,并未显示统计学显著差异[31]。 一项结合10项研究的荟萃分析[32],共纳入82,573例使用乳腺数字和屏-片X线检查进行筛查的女性,并对两种筛查结果进行对比。随机效应模型分析显示两种不同的筛查手段在肿瘤检出率方面并无统计学意义的差别(屏-片组的AUC为0.92,而数字组的AUC为0.91)。对于年龄小于50岁的女性,所有相关研究都显示数字乳腺X线摄影检查的敏感性更高,而特异性不低于应用乳腺屏-片X线检查。该荟萃分析中纳入的一项大型美国队列研究[33]发现对于年龄小于50岁的女性而言,乳腺屏-片和数字乳腺X线摄影的敏感性分别为75.7%(95%CI,71.7-79.3)和82.4%(95%CI,76.3-87.5);特异性分别为89.7%(95%CI,89.6-89.8)和88.0%(95%CI,87.8-88.2)。荟萃分析未发现其他年龄差异。

一项荷兰单中心人群筛查项目比较了50-75岁女性接受全视野数字乳腺X线摄影检查(FFDM)的结果,其中FFDM包括对SFM筛查女性进行计算机辅助检测(CAD)。5年内,共进行过311,082例SFM筛查和56,518例FFDM筛查。虽然两组并非随机分组,但参与者无明显偏倚。FFDM组的召回率高于SFM组,但两组的侵袭性乳腺癌检出率无差异。FFDM组导管内原位癌的检出率升高,与簇状微钙化检出率增高相关[34]

对10项不同设计的对照研究进行总结,发现总体上数字乳腺X线摄影检查提高乳腺癌的检出率(包括侵袭性癌与DCIS),但两种检查方法的召回率并无一致结果[35]

计算机X-线成像技术(CR)使用可移动暗箱式检测仪和外源性阅片设备以获取数字化影像。一项同期大型多队列研究共纳入254,758例FFDM筛查,487,334例SFM筛查,74,190例CR筛查结[36]。同样,结果显示虽然FFDM组的召回率较高,但FFDM组和SFM组的肿瘤检出率分别为每1,000例中检出4.9例和4.8例,并无差别。更为重要的时,CR组的肿瘤检出率为每1,000例中检出3.4例,低于前两组;其调整后的OR值为0.79(95%CI,0.68-0.93)。此前两项非同期队列研究显示,CR组与SFM组的肿瘤检出率并无差异,且CR组的肿瘤检出率并无提高[37][38]

乳腺X线摄影及CAD

CAD系统通过放大可疑区域,如簇状微钙化和肿块,以辅助影像科医师阅读乳腺X线摄影的结果[39]。CAD系统通常会增加摄片的敏感性、降低特异性[40],并提高导管内原位癌的检出率[41]。目前已有部分CAD系统正在应用之中。一项基于人群的大型研究对比了引入CAD系统前后,筛查召回率及乳腺癌检出率的差异,而结果显示并无差别[39][42]。另一项类似的大型研究发现引入CAD系统后,召回率及DCIS检出率均有所上升,而浸润性乳腺癌的检出率并无改变[41][43]

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