中国女性乳腺癌筛查与早诊早治指南(2021,北京)
中华肿瘤杂志, 2021,43(4) : 357-382. DOI: 10.3760/cma.j.cn112152-20210119-00061
一、引言

乳腺癌是女性常见的恶性肿瘤,其发病率和死亡率分别位列我国女性恶性肿瘤的第1位和第4位。2015年我国女性乳腺癌新发病例约30.4万例,占女性全部恶性肿瘤发病的17.1%;死亡病例约7.0万例,占女性全部恶性肿瘤死亡的8.2%[1,2]。近年来,随着我国人口老龄化的加速,工业化、城市化以及生活方式的改变,女性乳腺癌疾病负担日益加重[3,4]。提高早期乳腺癌的检出率并进行及时有效的治疗是降低乳腺癌死亡率的有效措施。多个国家(如美国、德国、日本和澳大利亚等)已陆续开展人群乳腺癌筛查。我国现已开展包括乳腺癌筛查在内的多个国家重大公共卫生服务项目,如城市癌症早诊早治项目、全国农村妇女"两癌筛查"项目等,均取得了较好的社会效益[5,6]

美国医师协会、美国预防服务工作组(U.S. Preventive Services Task Force, USPSTF)、美国国立综合癌症网络(National Comprehensive Cancer Network, NCCN)、加拿大预防保健工作组等多个在世界上有影响力的学术组织和机构分别制定了各自的乳腺癌筛查指南[7,8,9,10],中国抗癌协会在2019年发布了《中国女性乳腺癌筛查指南》和《乳腺癌诊治指南与规范(2019年版)》[11,12]。作为当前医疗实践中最常用的指导性文件,指南的发布与更新对提高应用决策的科学性和规范性发挥着重要的推动作用。高质量的指南是降低医疗成本和经济负担、改善医疗资源分布不均的有效工具,是规范医疗行为和提高医疗服务整体水平的重要手段[13,14,15]。为实现对潜在乳腺癌患者的早发现、早诊断、早治疗,提高筛查的科学性、可行性和适用性,制定符合我国国情的乳腺癌筛查与早诊早治指南是十分重要和必要的。

鉴于此,受国家卫生健康委员会疾病预防控制局的委托和指导,国家癌症中心按照循证实践指南制定的方法和步骤[16],基于最新的研究证据,结合我国乳腺癌筛查实际情况,制定了《中国女性乳腺癌筛查与早诊早治指南(2021,北京)》(以下简称本指南)。

二、指南形成流程

本指南的设计与制定步骤参照世界卫生组织(World Health Organization, WHO)2014年发布的《世界卫生组织指南制定手册》,并根据国际实践指南报告规范(Reporting Items for Practice Guidelines in Healthcare, RIGHT)和指南研究与评价工具(AGREE Ⅱ)进行报告[17,18]

1.指南发起机构与专家组成员:

本指南由国家癌症中心发起。指南制定启动时间为2020年4月1日,定稿时间为2020年12月23日。

2.指南工作组:

本指南成立多学科工作组,主要涵盖肿瘤学、流行病学、超声学、乳腺内科、乳腺外科、放射治疗学、病理学、循证医学、卫生经济学、健康管理和政策研究等相关学科。证据的检索和评价由兰州大学和国家癌症中心合作完成。所有工作组成员均填写了利益声明表,与本指南不存在利益冲突。

3.指南使用者与目标人群:

本指南适用于各级医疗机构开展乳腺癌筛查工作。指南的使用者为各级医疗机构的医务工作者,包括影像科、乳腺外科等筛查相关学科医师及工作人员。指南推荐意见的应用目标人群为中国40岁及以上女性。

4.临床问题的遴选和确定:

本指南工作组通过系统查阅国内外乳腺癌筛查领域已发表的系统评价和指南,以及对全国28个省、自治区、直辖市各专业的95位临床医师开展第1轮问卷调研,初步拟定了30个临床问题。第2轮问卷调查邀请全国50位具有高级职称的临床医师对拟定临床问题进行重要性评价,并通过指南指导委员会会议,最终遴选出本指南拟解决的16个问题。

5.证据的检索:

指南制定工作组成立了证据检索与评价小组,针对最终纳入的关键临床问题,按照人群、干预、对照和结局原则对其进行中英文数据库检索。具体检索数据库包括PubMed、EMBASE、Cochrane Library、Web of Science、UpToDate、DynaMed、英国国家卫生与临床优化研究所(National Institute for Health and Care Excellence,NICE)、苏格兰校际指南网络、中国知网、万方数据库、维普资讯网、中国生物医学文献数据库和WHO临床试验注册平台,同时利用数据库的相似文献功能追踪乳腺癌筛查相关综述和系统评价/Meta分析的参考文献,继续补充检索。数据检索截止日期为2020年6月26日,检索策略见附件A。

6.证据的评价与分级:

证据检索与评价小组运用系统评价偏倚风险评价工具对纳入的系统评价、Meta分析进行偏倚风险评价[19,20]。使用Cochrane Reviewer′s Handbook 5.0.1偏倚风险评价工具、诊断准确性研究的质量评价工具和纽卡斯尔-渥太华量表等对相应类型的原始研究进行偏倚风险评价[21,22,23]。使用推荐意见分级的评估、制定及评价方法(Grading of Recommendations Assessment, Development and Evaluation, GRADE)对证据体进行分级[24,25],证据质量分级方法见表1。评价过程由两人独立完成,若存在分歧,则共同讨论或咨询第三方解决。

点击查看表格
表1

GRADE证据质量与推荐强度分级

表1

GRADE证据质量与推荐强度分级

项目 内容
证据质量指在多大程度上能够确信预测值的正确性  
  高(A) 非常有把握:观察值接近真实值
  中(B) 有中等把握:观察值有可能接近真实值,但亦有可能差别很大
  低(C) 把握有限:观察值可能与真实值有较大差别
  极低(D) 几乎没有把握:观察值可能与真实值有极大差别
推荐强度指在一定程度上能够相对明确推荐意见的利弊  
  强(1) 当前证据能够相对明确提示干预措施利大于弊或弊大于利
  弱(2) 当前证据尚不足以明确筛查的利弊,或提示利弊相当
7.推荐意见的形成:

专家组针对基于证据检索与评价小组提供的临床问题进行系统评价,并基于证据给出推荐意见,同时考虑我国患者的偏好与价值观、干预措施的成本和利弊后,提出了符合我国筛查实践的推荐意见,分别于2020年9月10日和2020年10月10日进行2轮德尔菲推荐意见调查,共收集到166条反馈建议,于2020年11月13日进行面对面商议并于2020年12月进一步修改,形成了本指南的推荐意见。本指南中的推荐强度指在一定程度上能够相对明确推荐意见的利弊,其中强(1):当前证据能够相对明确提示干预措施利大于弊或弊大于利;弱(2):当前证据尚不足以明确筛查的利弊,或提示利弊相当[26](表1)。

8.指南文稿的形成与外审:

本指南工作组参考RIGHT报告规范草拟指南文稿,内部审议后形成征求意见稿。通过在国家癌症中心组织的会议等方式公开征求意见,并送期刊外审的形式收集修改意见,根据反馈结果完善形成最终稿。

9.指南的传播、实施与更新:

指南发布后,本指南工作组将主要通过以下方式对指南进行传播和推广:(1)在相关学术会议中对指南进行解读;(2)有计划地在中国部分省份组织指南推广专场会议,确保基层的恶性肿瘤筛查工作人员充分了解并正确应用本指南;(3)在学术期刊和书籍出版社公开发表本指南;(4)通过媒体等进行推广。指南工作组将综合临床实践需求与证据现状,并参考更新版指南报告清单,对本指南进行更新。计划每3年对本指南的推荐意见进行更新。

三、关键问题及推荐意见
(一)流行病学特征

问题1:我国女性乳腺癌发病率、死亡率和生存率情况

(A)我国女性乳腺癌负担重,是女性恶性肿瘤死亡的主要原因之一

(B)我国女性乳腺癌发病率呈上升趋势,并呈现出地区、年龄差异

(C)我国女性乳腺癌死亡率呈上升趋势,并呈现出地区、年龄差异

(D)我国女性乳腺癌5年相对生存率近年来有所升高

2020年中国女性乳腺癌发病率为59.0/10万,居全国女性恶性肿瘤发病谱首位[27]。国家癌症中心公布的数据显示,2015年中国女性乳腺癌新发病例为30.4万例,占女性恶性肿瘤新发病例数的17.1%。不同地域女性乳腺癌发病率存在差异,总体为城市乳腺癌发病率(54.3/10万)高于农村(33.6/10万),女性乳腺癌发病率在城市和农村分别位列女性恶性肿瘤发病率首位和第2位[2]。不同地区之间女性乳腺癌发病率也存在差异(东部>中部>西部),2015年中国东部地区女性新发乳腺癌14.6万例,发病率为57.4/10万;中部地区新发病例9.5万例,发病率为42.4/10万;西部地区新发病例6.3万例,发病率为32.7/10万,女性乳腺癌发病率分别位列东、中和西部地区女性恶性肿瘤发病的第1位、第1位和第2位[28]。我国女性乳腺癌发病率呈上升趋势[4,29],2000—2014年各年份肿瘤登记地区的女性乳腺癌年龄别发病率分析结果显示,各年龄组女性乳腺癌发病率均有所上升,乳腺癌发病高峰年龄主要集中在50~59岁之间[30]

2020年中国女性乳腺癌死亡率为16.6/10万,居全国女性恶性肿瘤死亡谱第4位[27]。根据国家癌症中心公布的数据显示,2015年中国女性乳腺癌死亡病例7.0万例。不同地域女性乳腺癌死亡率存在差异,总体城市女性乳腺癌死亡率(12.2/10万)高于农村(8.4/10万),女性乳腺癌死亡率在城市和农村分别位列女性恶性肿瘤死亡第3位和第6位[2]。不同地区之间女性乳腺癌死亡率也存在差异,2015年中国东部地区女性乳腺癌死亡病例3.1万例,死亡率为12.0/10万;中部地区死亡病例2.4万例,死亡率为10.8/10万;西部地区死亡病例1.6万例,死亡率为8.2/10万,女性乳腺癌死亡率在东、中和西部地区分别位列女性恶性肿瘤死亡的第4位、第4位和第5位[28]。我国女性乳腺癌死亡率呈上升趋势[4,31,32]。乳腺癌年龄别死亡率随年龄的增长而上升,在85岁以上年龄组达到最高[29],国家癌症中心数据显示,2014年85岁以上年龄组女性乳腺癌死亡率高达52.8/10万[33]

2003—2015年全国17个肿瘤登记地区数据显示,女性乳腺癌5年合计相对生存率从73.1%(95% CI:71.2%~75.0%)增长至82.0%(95% CI:81.0%~83.0%);城市地区和农村地区2012—2015年女性乳腺癌5年相对生存率分别为84.9%和72.9%[34]

问题2:乳腺癌相关危险因素和保护因素

危险因素

(A)部分良性乳腺疾病患者的乳腺癌发生风险高

(B)子宫内膜异位症增加乳腺癌的发病风险

(C)高内源性雌激素水平会增加乳腺癌的发病风险

(D)特定的月经生育因素与乳腺癌发病相关

(E)乳腺癌家族史是乳腺癌的危险因素

(F)乳腺癌易感基因(breast cancer susceptibility genes, BRCA)1/2突变与乳腺癌发病相关

(G)肥胖是乳腺癌的危险因素

(H)大量饮酒是乳腺癌的危险因素

(I)吸烟是乳腺癌的危险因素

(J)暴露于治疗性电离辐射的女性乳腺癌发病风险增高

保护因素

(A)母乳喂养可以降低乳腺癌的发病风险

(B)适宜的体育锻炼可以降低乳腺癌的发病风险

1.目前研究已明确的危险因素

(1)良性乳腺疾病:部分良性乳腺疾病(如乳腺囊肿和乳腺上皮不典型增生等)患者的乳腺癌发病风险增高[35,36,37]。李红等[35]对2002—2012年发表的良性乳腺疾病与乳腺癌关系的7项研究进行Meta分析,结果显示,良性乳腺疾病者患乳腺癌的风险为无良性乳腺疾病者的2.24倍(OR:2.24,95% CI:1.23~4.09)。戴琼等[36]对1997—2007年发表的良性乳腺疾病与乳腺癌关系的31项研究(16 611例)进行Meta分析,结果显示,良性乳腺疾病者患乳腺癌的风险为无良性乳腺疾病者的1.95倍(OR:1.95,95% CI:1.59~2.38)。裴广军等[37]对1996—2006年发表的良性乳腺疾病与乳腺癌关系的12项病例对照研究进行Meta分析,结果显示,良性乳腺疾病者患乳腺癌的风险为无良性乳腺疾病者的2.62倍(OR:2.62,95% CI:2.03~3.38)。

(2)子宫内膜异位症:子宫内膜异位症是乳腺癌的危险因素。Kvaskoff等[38]对1993—2019年子宫内膜异位症和乳腺癌关系的20项研究进行Meta分析,结果显示,子宫内膜异位症者患乳腺癌的风险为无子宫内膜异位症者的1.04倍(RR:1.04,95% CI:1.00~1.09)。

(3)高内源性雌激素水平:无论是绝经前还是绝经后女性,高内源性雌激素水平均会增加乳腺癌的发病风险。Key等[39]对18项前瞻性研究进行的Meta分析和Farhat等[40]的研究表明,对于绝经后女性,激素水平上升与乳腺癌发病风险呈正相关。有学者汇总分析了7项前瞻性研究,共纳入767例绝经前乳腺癌女性和1 699例匹配对照者,结果显示,乳腺癌患病风险与雌二醇(OR:1.19,95% CI:1.06~1.35)、游离雌二醇(OR:1.17,95% CI:1.03~1.33)、雌激素酮(OR:1.27,95% CI:1.05~1.54)、雄烯二酮(OR:1.30,95% CI:1.10~1.55)、硫酸脱氢表雄酮(OR:1.17,95% CI:1.04~1.32)和睾酮(OR:1.18,95% CI:1.03~1.35)浓度呈正相关[41]

(4)月经生育因素:①初潮较早或绝经较晚:初潮年龄较早与乳腺癌发生风险较高有关。15岁或之后初潮的女性患雌激素受体和(或)孕激素受体阳性乳腺癌的风险低于13岁之前初潮的女性(HR:0.76,95% CI:0.68~0.85)[42]。Cui等[43]进行的一项基于美国人群的病例对照研究显示,初潮年龄≥14岁患乳腺癌的风险降低(OR:0.70,95% CI:0.55~0.88)。一项纳入117项研究的个体病例数据Meta分析结果显示,初潮每推迟1年,乳腺癌风险下降5%[44]。此外,一项纳入了51篇文献的研究结果显示,在从未接受过激素治疗的人群中,绝经年龄每推迟1年,患乳腺癌的相对危险度增加3%(RR:1.03,95% CI:1.02~1.03)[45]。②未经产与初次妊娠的年龄较高:未经产和初次妊娠较晚的女性患乳腺癌的风险增加。一项研究显示,未经产女性患乳腺癌的风险是经产女性的1.32倍(OR:1.32,95% CI:1.06~1.63)[43]。在绝经期或接近绝经期的女性中,与未经产女性相比,首次生产年龄为20岁、25岁和35岁女性乳腺癌的累积发病率(直到70岁)分别降低20%、10%和升高5%[44]。③流产:一篇针对有人工流产史中国女性的Meta分析共纳入36篇文献,结果显示,与没有人工流产史的女性相比,有人工流产的女性患乳腺癌的风险增加44%(OR:1.44,95% CI:1.29~1.59),对于人工流产达到2次或2次以上的女性,患乳腺癌风险分别增加76%和89%[46]

(5)乳腺癌家族史:Nindrea等[47]对纳入的10项研究进行Meta分析,结果显示,有乳腺癌家族史人群患乳腺癌的风险为正常人群的3.34倍(OR:3.34,95% CI:2.68~4.15);Vishwakarma等[48]对纳入的21 511例乳腺癌患者进行分析,结果显示,有乳腺癌家族史的人群乳腺癌发病风险为健康人群的5.33倍(OR:5.33,95% CI:2.89~9.82)。

(6)基因突变:BRCA增加乳腺癌发病风险。具有BRCA1/2致病性突变的患者发生乳腺癌、卵巢癌和其他恶性肿瘤的风险增加。对于BRCA1突变携带者,≤70岁时乳腺癌累积风险为55%~70%,BRCA2突变携带者的相应累积风险为45%~70%。此外,BRCA1突变携带者从成年早期到30~40岁时的乳腺癌发生率升高,BRCA2突变携带者从成年早期到40~50岁时的乳腺癌发生率升高,此后至80岁为平台期,乳腺癌发生率为20~30/1 000人年[49,50,51,52]。与BRCA2突变携带者或BRCA1/2突变阴性者相比,BRCA1突变携带者更可能发生三阴性乳腺癌[53,54]。Guo等[55]在一项Meta分析中指出,BRCA1启动子高甲基化人群患乳腺癌的风险为一般人群的1.76倍(HR:1.76,95% CI:1.15~2.68)。

(7)肥胖:一项纳入了12项观察性研究的系统评价和Meta分析结果显示,在队列研究中脂肪含量最高的人群患乳腺癌风险为脂肪含量最低的人群的1.44倍(RR:1.44,95% CI:1.33~1.56)[56]。世界癌症研究基金会(World Cancer Research Fund, WCRF)和美国癌症研究所(American Institute for Cancer Research, AICR)在2018年发布的癌症预防报告(第3版)[57]中汇总了肥胖与绝经前或绝经后女性乳腺癌发病风险的相关证据,大量流行病学证据和剂量-反应关系分析支持同样的结论,即肥胖会增加绝经后女性乳腺癌的发病风险。

(8)生活方式因素:①饮酒:饮酒人群的乳腺癌发病风险增高[57,58,59,60,61,62,63]。WCRF/AICR[57]共纳入10项研究对绝经前乳腺癌发病风险进行剂量-反应Meta分析,结果显示,每天摄入10 g酒精可使乳腺癌发病风险增加5%(RR:1.05,95 %CI:1.02~1.08);对绝经后乳腺癌发病风险的剂量-反应Meta分析纳入22项研究,结果显示,每天摄入10 g酒精可使乳腺癌发病风险增加9%(RR:1.09,95% CI:1.07~1.12)。陶苹等[63]对纳入的27项研究进行Meta分析,结果显示,有饮酒史人群患乳腺癌的风险为无饮酒史人群的1.16倍(OR:1.16,95% CI:1.01~1.32)。Bagnardi等[58]对纳入的118项研究进行Meta分析,结果显示,重度饮酒人群患乳腺癌的风险为不饮酒和偶尔饮酒人群的1.61倍(RR:1.61,95% CI:1.33~1.94)。②吸烟:吸烟人群乳腺癌的发病风险增高[62,63,64,65,66]。美国卫生与公众服务部于2014年系统汇总了吸烟与乳腺癌发病风险的相关证据,纳入22项队列研究和27项病例对照研究,结果显示,曾经吸烟使乳腺癌发病风险升高10%。吸烟时间长(20年或以上),每天吸烟量多(20支或以上),则使乳腺癌发病风险增加13%~16%[64]。陶苹等[63]对纳入的27项研究进行Meta分析,结果显示,有吸烟史人群患乳腺癌的风险为无吸烟史人群的1.50倍(OR:1.50,95% CI:1.03~2.20)。Gaudet等[65]在美国癌症协会癌症预防研究的一项队列研究中发现,正在吸烟人群的乳腺癌发病率为非吸烟人群的1.24倍(HR:1.24,95% CI:1.07~1.42),有吸烟史人群的乳腺癌发病率为非吸烟人群的1.13倍(HR:1.13,95% CI:1.06~1.21)。

(9)暴露于治疗性电离辐射:暴露于治疗性电离辐射的女性患乳腺癌的风险增高[67,68,69]。Ron[67]的研究显示,行多次胸部透视检查的女性肺结核患者患乳腺癌的风险增加。年轻时胸部暴露于电离辐射如接受过放射治疗的霍奇金淋巴瘤的女性,其患乳腺癌的风险增加,且女童肿瘤患者接受高剂量放疗后乳腺癌标化发病率比为24.20(95% CI:20.70~28.30)[68]。另一项研究显示,乳腺癌的发病风险随胸部放射剂量呈线性增加,与乳腺癌发病风险相关的电离辐射因素包括照射时的年龄、照射持续时间和辐射剂量等[69]

2.目前研究已明确的保护因素

(1)母乳喂养:现有研究表明,母乳喂养可以降低乳腺癌的发病风险[70,71,72,73]。一项评估母乳喂养对孕产妇健康结果影响的系统评价提示,12个月母乳喂养可使乳腺癌的患病风险降低26%(OR:0.74,95% CI:0.69~0.79),说明母乳喂养是乳腺癌的保护因素[70]。与从不母乳喂养者相比,曾经母乳喂养者乳腺癌的患病风险下降22%(OR:0.78,95% CI:0.74~0.82),母乳喂养<6个月和母乳喂养6~12个月者乳腺癌的患病风险分别降低7%(OR:0.93,95% CI:0.88~0.99)和9%(OR:0.91,95% CI:0.87~0.96)。Victora等[71]的研究显示,母乳喂养可以预防乳腺癌,将母乳喂养普及化后,每年可减少20 000名因乳腺癌死亡的患者。Shamshirian等[72]的Meta分析结果显示,13~24个月的母乳喂养是乳腺癌的保护因素(OR:0.68,95% CI:0.46~0.90)。一项纳入24篇研究的Meta分析结果显示,累计母乳喂养较长时间,与乳腺癌的患病风险呈负相关(RR:0.47,95% CI:0.37~0.60)[73]

(2)体育锻炼:流行病学研究证据显示,适宜的体育锻炼可以降低女性乳腺癌的发病风险[57,74,75]。WCRF/AICR在2018年发布的癌症预防报告(第3版)共纳入4项研究对体育锻炼和绝经前乳腺癌的发病风险进行Meta分析,结果显示,体育锻炼和绝经前乳腺癌的发病差异无统计学意义(RR:0.93,95% CI:0.79~1.08),体育锻炼对降低绝经前乳腺癌的发病风险证据有限。在体育锻炼对绝经后乳腺癌发病风险影响的Meta分析中,共纳入8项研究,结果显示,高水平体育锻炼可使绝经后乳腺癌的发病风险降低13%(RR:0.87,95% CI:0.79~0.96)[57]。McTiernan等[74]的研究显示,与缺乏体育锻炼的女性相比,定期进行体育锻炼的女性乳腺癌的发病风险降低14%(RR:0.86,95% CI:0.78~0.95)。2016年的一篇针对38项前瞻性研究的Meta分析提示,与缺乏体育锻炼的女性相比,积极进行体育锻炼的女性乳腺癌的发病风险下降12%(RR:0.88,95% CI:0.85~0.90)[75]

(二)结局和定义

问题3:筛查相关的乳腺癌病理分型和TNM分期

(A)乳腺癌的组织学分型包括:(1)非浸润性癌:导管原位癌、小叶原位癌;(2)浸润性癌:浸润性癌非特殊型、浸润性小叶癌、小管癌、黏液癌等

(B)根据美国癌症联合会(American Joint Committee on Cancer, AJCC)TNM分期系统(第8版),乳腺癌分为0期、Ⅰ期、Ⅱ期、Ⅲ期和Ⅳ期

乳腺癌的组织学分型推荐采用WHO乳腺肿瘤分类标准(2019年版)[76]

乳腺癌分期系统推荐应用AJCC第8版(表2)[77]。细化定义如下。

点击查看表格
表2

美国癌症联合会TNM分期对应表

表2

美国癌症联合会TNM分期对应表

TNM分期 T N M
0 Tis N0 M0
ⅠA T1 N0 M0
ⅠB T0 N1mi M0
T1 N1mi M0
ⅡA T0 N1 M0
T1 N1 M0
T2 N0 M0
ⅡB T2 N1 M0
T3 N0 M0
ⅢA T0 N2 M0
T1 N2 M0
T2 N2 M0
T3 N1 M0
T3 N2 M0
ⅢB T4 N0 M0
T4 N1 M0
T4 N2 M0
ⅢC 任何T N3 M0
任何T 任何N M1

(1)原发性肿瘤(T):TX:原发性肿瘤无法评估;T0:无原发性肿瘤证据;Tis:原位癌;T1:肿瘤最大径≤20 mm;T2:肿瘤最大径>20 mm但≤50 mm;T3:肿瘤最大径>50 mm;T4:肿瘤直接侵袭胸壁和(或)皮肤(溃疡或肉眼可见的皮肤结节),不论大小。

(2)区域淋巴结(N):pNX:区域淋巴结无法评估(先前已切除,或未切除进行病理学检查);pN0:无区域淋巴结转移证据;pN1mi:微转移(单枚淋巴结单张肿瘤切片中,肿瘤最大径>0.2 mm和(或)多于200个细胞,但≤2.0 mm);pN1a:1~3枚腋窝淋巴结转移,至少1枚转移灶>2.0 mm;pN1b:在没有腋窝淋巴结转移的情况下,同侧内乳前哨淋巴结转移,且转移灶>0.2 mm,孤立的肿瘤细胞群除外;pN1c:同时出现pN1a和pN1b;pN2:4~9枚腋窝淋巴结转移,或影像学检查显示同侧内乳淋巴结转移而无腋窝淋巴结转移;pN3:10枚或更多腋窝淋巴结转移(至少1枚转移灶>2.0 mm);或锁骨下淋巴结(属第Ⅲ水平腋窝淋巴结)转移(pN3a);或影像学检查显示同侧内乳淋巴结转移,伴1枚或多枚Ⅰ、Ⅱ级腋窝淋巴结转移;或3枚以上腋窝淋巴结转移,以及前哨淋巴结活检证实但临床未发现的内乳淋巴结微转移灶或宏转移灶(pN3b);或同侧锁骨上淋巴结转移(pN3c)。

(3)远处转移(M):M0:没有远处转移的临床或放射影像学证据;M1:临床和放射影像学方法确定和(或)组织学证实存在>0.2 mm的远处转移灶。

问题4:乳腺早期癌和癌前病变定义

(A)乳腺早期癌指肿瘤直径<2 cm,同侧腋窝淋巴结未见转移,且无远处转移

(B)乳腺癌前病变包括小叶肿瘤(不典型小叶增生)、柱状细胞病变(扁平上皮不典型增生)和导管上皮不典型增生

早期乳腺癌和癌前病变定义主要参考来源包括WHO乳腺肿瘤分类(2019年版)、中国女性乳腺癌筛查指南和中国抗癌协会乳腺癌诊治指南与规范(2019年版)等多部国内外指南和专家共识[11,12,76]

问题5:筛查的危害

(A)筛查的危害是指与未筛查相比,个人或群体在参与筛查过程中产生的任何负面效应

(B)过度诊断是指发现一种病变,即便它没有被诊断,也不会导致疾病发病率或死亡率的增加。假阳性是指根据筛查结果而推荐进行后续其他诊断性检查(包括进一步的影像学检查或组织取样检查),但在其后1年内未查出乳腺癌的情况;以及部分被诊断的恶性肿瘤,即使未接受临床治疗,终生也不会死于该恶性肿瘤的情况

(C)假阳性结果导致的压力:筛查个体得到假阳性结果后,由于压力导致产生的焦虑、抑郁、沮丧等负面情绪

(D)其他:乳腺X线检查所带来的躯体不适或疼痛导致人群筛查依从性降低

(E)假阴性漏诊导致的负面效应

乳腺癌筛查的危害主要参考UpToDate数据库《乳腺癌筛查的策略与推荐》[78]、《乳腺癌筛查:效果和危害的证据》[79]以及NCCN和USPSTF发布的乳腺癌筛查指南[7,10]。具体包括以下。

(1)筛查的危害:乳腺癌筛查的危害包括过度诊断、假阳性结果、患者焦虑和不必要的治疗及其风险。乳腺癌筛查最严重的危害是过度诊断、假阳性结果。

(2)过度诊断:筛查的过度诊断是指通过筛查手段发现的早期恶性肿瘤患者,其中部分恶性肿瘤并不会继续生长、转移并导致患者死亡。这些患者如果不通过筛查发现,就不会在临床上出现有重要意义的疾病诊断。过度诊断会导致不必要的检查和治疗,以及恶性肿瘤诊断和治疗的心理负担和其他后果。在所有诊断为乳腺癌的女性中,过度诊断率从≤10%到>50%不等[80,81]。这些差异可能来源于研究设计不同,比如各研究纳入的研究对象不同(如是否纳入乳腺导管内原位癌、纳入研究的年龄段)、使用的测量和估算的方法不同等。过度诊断使某些患者接受了针对恶性肿瘤的治疗,但恶性肿瘤未被发现也不会造成伤害,从而使得筛查既带来不利影响(躯体和心理)也未降低死亡率。

(3)假阳性结果:增加假阳性风险的因素包括:年轻、乳腺密度高、乳腺癌家族史或个人史、既往乳腺活检、正在使用雌激素、较短的筛查间隔、未与之前检查结果对比以及放射科医师个人的过度解读倾向[82,83]。假阳性结果在较年轻女性中更常见,因为这类人群中乳腺X线摄影的特异性较低[84]。此外,因为乳腺癌常规筛查推荐每年或隔年进行复查,所以假阳性风险会随着复查频率而升高,并且相较于每2年1次的筛查,每年1次的筛查会使这一风险升高更快[85]

(4)假阳性结果相关性焦虑:一项Meta分析显示,乳腺X线摄影结果为假阳性后的焦虑是针对乳腺癌和乳腺X线摄影,不会导致广泛性焦虑障碍[83]。有关假阳性乳腺筛查结果对以后筛查行为的影响,报道结果各异,如美国女性在出现1次假阳性筛查结果后进行常规筛查的可能性更高,但假阳性筛查结果对欧洲女性没有影响[83]。虽然乳腺X线摄影出现假阳性结果可能导致对卫生保健资源的浪费[86],但有关假阳性结果对医疗的信任度和卫生保健服务利用情况的影响还需进一步研究。

(5)辐射:如果每年乳腺筛查中接受1次乳腺X线摄影,据估计,一生中辐射诱导恶性肿瘤导致的女性死亡率为16/10万[87]。乳房较大的女性发生辐射诱导乳腺癌的风险可能更高。

(6)不适:由于需要挤压乳房以获取满意的图像,乳腺X线摄影筛查可引起不适或疼痛。目前有关减轻不适方法的高质量研究很少[88]。一项随机试验纳入了操作很可能引发其疼痛的女性,结果显示,在乳房和胸壁局部涂敷4%利多卡因凝胶可减少不适,但对乙酰氨基酚或布洛芬前期用药则没有这种效果[89]。减轻不适感可增加患者返回进行下一次筛查的意愿。

(7)假阴性结果导致的负面效应:由于筛查的手段对于乳腺癌检出概率并不能达到100%[90]

(三)筛查人群风险分类

问题6:一般风险人群定义

推荐意见:一般风险人群:乳腺癌一般风险女性即除了乳腺癌高风险人群(见问题7)以外的所有适龄女性

问题7:高风险人群定义

推荐意见:高风险人群:符合下列(1)、(2)和(3)任意条件的女性为乳腺癌高风险人群

(1)有遗传家族史,即具备以下任意一项者:①一级亲属有乳腺癌或卵巢癌史;②二级亲属50岁前,患乳腺癌2人及以上;③二级亲属50岁前,患卵巢癌2人及以上;④至少1位一级亲属携带已知BRCA1/2基因致病性遗传突变;或自身携带BRCA1/2基因致病性遗传突变。

(2)具备以下任意一项者:①月经初潮年龄≤12岁;②绝经年龄≥55岁;③有乳腺活检史或乳腺良性疾病手术史,或病理证实的乳腺(小叶或导管)不典型增生病史;④使用"雌孕激素联合"的激素替代治疗不少于半年;⑤45岁后乳腺X线检查提示乳腺实质(或乳房密度)类型为不均匀致密型或致密型。

(3)具备以下任意两项者:①无哺乳史或哺乳时间<4个月;②无活产史(含从未生育、流产、死胎)或初次活产年龄≥30岁;③仅使用"雌激素"的激素替代治疗不少于半年;④流产(含自然流产和人工流产)≥2次。

注:一级亲属指母亲、女儿以及姐妹;二级亲属指姑、姨、祖母和外祖母

一般风险人群指患癌风险处于平均或较低水平的人群。目前关于一般风险人群的定义在全球各国所制定的乳腺癌筛查指南或共识中的标准有一定的差异,详见表3。大多数指南将乳腺癌终生风险作为判定风险程度的一个重要指标。例如,国际癌症研究机构(International Agency for Research on Cancer, IARC)[91]、NICE[92]、美国放射学会(American College of Radiology, ACR)[93]和乳腺家族史外科协会指南小组(Association of Breast Surgery Family History Guidelines Panel, ABSFHGP)[94]均将乳腺癌终生风险作为判定风险程度的一个重要指标,对于有乳腺癌、卵巢癌、输卵管癌或腹膜癌家族史的女性,USPSTF推荐了5种简明筛查工具,用于确定哪些女性需要接受遗传咨询、致病型BRCA1和BRCA2基因突变检测以及考虑化学预防、预防性手术和筛查推荐[95,96]。推荐的模型包括安大略家族史风险评估量表[97]、曼彻斯特评分系统[98]、转诊筛查量表[99]、系谱评估量表[100]和7条目家族史筛查量表[101]

点击查看表格
表3

国外指南中对乳腺癌一般风险人群定义汇总

表3

国外指南中对乳腺癌一般风险人群定义汇总

提出组织/机构 时间 适用人群 一般风险人群定义
国际癌症研究机构[91] 2015年 通用 乳腺癌终生风险<15%
英国国家卫生与临床优化研究所[92] 2017年 通用 乳腺癌终生风险<17%
美国放射协会[93] 2017年 美国 乳腺癌终生风险<15%
乳腺家族史外科协会指南小组[94] 2004年 英国 乳腺癌终生风险<1∶6
美国癌症协会[102]  2015年 美国 无以下风险因素的人群:
        乳腺癌个人史
        确认或疑似增加患乳腺癌风险的女性(例如BRCA1/2)基因突变
        曾对胸部进行过放射治疗的病史
美国医师学会[103] 2019年 美国 无乳腺癌的个人病史
无高危乳腺病变的诊断
儿童时期未接受过胸部放射治疗

注:BRCA:乳腺癌易感基因

全球各国家的乳腺癌筛查指南中对于高风险人群的定义或标准有一定差异(表4)。除奥克兰放射协会(Auckland Radiology Group, ARG)[104]外,其他指南都将发生乳腺癌的终生风险作为衡量高危风险人群的一个标准,但仍有不同。IARC的指南[91]中指出欧洲和美国的标准分别是30%和20%,加拿大安大略癌症治疗中心(Cancer Care Ontario,CCO)[105]与ABSFHGP[94]将该标准权重同定为25%。乳腺癌家族史、胸部放射治疗史、携带BRCA基因的人群及其一级亲属被ACR[93]、CCO[105]和ARG[104]定义为高风险人群。

点击查看表格
表4

国外指南中对乳腺癌高风险人群定义汇总

表4

国外指南中对乳腺癌高风险人群定义汇总

提出组织/机构 时间 适用人群 高危风险人群定义
国际癌症研究机构[91]  2015年 通用 美国定义为发生乳腺癌的终生风险>20%,欧洲定义为发生乳腺癌的终生风险>30%
英国国家卫生与临床优化研究所[92] 2017年 通用 发生乳腺癌的终生风险>30%
美国放射协会[93] 2017年 美国 具备遗传因素导致患乳腺癌风险增加的女性
有胸部放疗史(30岁之前累积放疗剂量≥10 Gy)
40岁以前被诊断为乳腺癌、导管上皮不典型增生或小叶肿瘤者
个人发生乳腺癌的终生风险>20%
乳腺家族史外科协会指南小组[94] 2004年 英国 乳腺癌终生风险>1∶4
奥克兰放射协会[104] 2007年 奥克兰 家族中有直系亲属曾患乳腺癌
有胸部放射治疗史
乳腺导管上皮不典型增生
活检时发现小叶原位癌
有乳腺癌疾病史
加拿大安大略癌症治疗中心[105] 2019年 加拿大 携带BRCA等基因
一级亲属携带有已知BRCA基因致病性遗传突变
有乳腺癌病史或既往活检中发现高危标志物
有胸部放射治疗史
有乳腺癌家族史且个人发生乳腺癌的终生风险>25%

注:BRCA:乳腺癌易感基因

(四)乳腺癌筛查起始年龄及筛查频次

问题8:乳腺癌筛查起始年龄

推荐意见8.1:对于一般风险人群,推荐从45岁开始进行乳腺癌筛查(强推荐,GRADE证据分级:中)

推荐意见8.2:对于高风险人群,推荐从40岁开始进行乳腺癌筛查(强推荐,GRADE证据分级:中)

推荐说明:根据我国国家癌症中心肿瘤登记数据,2015年,我国女性45岁起乳腺癌发病率呈上升趋势且维持在较高水平(图1),比西方女性乳腺癌高发年龄提前。出现45~55岁这个特定发病高峰的原因,有学者认为是出生队列效应影响。中国和日本等多数国家出生队列研究中普遍存在着月经和生育模式变化,加之其他生活方式和环境因素影响,这一效应使得乳腺癌发病风险因素在年龄较轻的女性中凸显[106,107]

点击查看大图
图1
2015年中国所有登记区域内女性乳腺癌年龄别发病率(数据来源国家癌症中心)
图1
2015年中国所有登记区域内女性乳腺癌年龄别发病率(数据来源国家癌症中心)

本指南证据检索与评价小组于2020年开展系统评价,对参与乳腺癌筛查人群的乳腺癌死亡率和乳腺癌发病率效果进行评价,共纳入8个试验,结果显示:(1)乳腺癌死亡率(n=671 346,8个试验):40~49岁年龄段筛查是否获益不确定(RR:0.89,95% CI:0.79~1.00),50~69岁年龄段筛查获益(50~59岁:RR:0.84,95% CI:0.73~0.96;60~69岁:RR:0.71, 95% CI:0.59~0.85),70~74岁年龄段筛查是否获益不确定(RR:0.80,95% CI:0.52~1.22)。(2)晚期乳腺癌发病率(n=444 744,4个试验):40~49岁年龄段晚期乳腺癌发病率无差异(RR:0.98,95% CI:0.74~1.28),对50岁以上人群筛查可降低晚期乳腺癌的发病率(RR:0.62,95% CI:0.47~0.80)[108,109,110,111,112,113,114,115]。证据级别均评为中等质量。鉴于所纳入的随机对照试验均源于欧美国家,结果外推需谨慎,而我国暂缺乏乳腺癌筛查大型人群随机对照试验结果。本指南制专家共识会议中,专家们综合考虑我国女性乳腺癌发病年龄、流行病学特征、相关危险因素和卫生经济学现况,推荐一般风险人群从45岁开始进行乳腺癌常规筛查,高风险人群筛查起始年龄提前至40岁。

问题9:乳腺癌筛查频次

推荐意见9.1:对于一般风险人群,推荐每1~2年进行1次乳腺癌筛查(强推荐,GRADE证据分级:中)

推荐意见9.2:对于高风险人群,推荐每年进行1次乳腺癌筛查(强推荐,GRADE证据分级:中)

推荐说明:本指南证据检索与评价小组于2020年开展了系统评价,对乳腺癌筛查频次对人群乳腺癌的死亡率、发病率、累积假阳性召回率和累积假阳性有创召回率的影响进行评价,共纳入13个研究,结果显示:(1)在乳腺癌死亡率比较中(n=934 113,4个研究[117,120,125,126]),筛查频次为2年1次或3年1次与1年1次,筛查结果差异无统计学意义(RR:1.04,95% CI:0.93~1.16);对于75岁以上人群,与2年筛查1次相比,筛查间隔>2年组患者死亡风险增加(RR:1.87,95% CI:1.34~2.61)。(2)在乳腺癌发病率比较中(n=1 278 256,7个研究),筛查频次为2年1次时,乳腺癌发病率相比1年1次时增高(RR:1.07,95% CI:1.04~1.10)。(3)在累积假阳性召回率和累积假阳性有创召回率的比较中(n=1 508 136,6个研究),2年1次筛查频次的10年累积假阳性召回率为32.07%(95% CI:20.69%~43.45%),累积假阳性有创召回率为4.79%(95% CI:3.81%~5.78%);1年1次筛查频次的10年累积假阳性召回率为49.96%(95% CI:36.09%~63.84%),累积假阳性有创召回率为8.73%(95% CI:7.31%~10.15%)。2年1次筛查较1年1次筛查,其乳腺癌死亡率、发病率略有增加,但假阳性召回率等相关风险降低[116,117,118,119,120,121,122,123,124,125,126,127,128]。证据级别均为中等质量。

(五)筛查措施

问题10:单独使用乳腺X线摄影筛查效果

推荐意见10.1:对于一般风险人群,可考虑使用乳腺X线摄影进行筛查(强推荐,GRADE证据分级:中)

推荐意见10.2:对于高风险人群,不推荐单独使用乳腺X线摄影进行筛查(强推荐,GRADE证据分级:低)

推荐说明:本指南证据检索与评价小组于2020年开展了系统评价,对乳腺X线摄影筛查乳腺癌对比诊断结果和随访结果的诊断准确性进行评价,共纳入87个研究。在所有人群中单独使用乳腺X线摄影进行筛查(n=1 191 809,87个研究):56个研究合并的灵敏度为80.00%(95% CI:75.00%~84.00%;31个无法合并研究的灵敏度介于33.60%~100.00%),56个研究合并的特异度为96.00%(95% CI:94.00%~97.00%;24个无法合并研究的特异度介于67.90%~99.10%),阳性似然比(positive likelihood ratio, LR+)为17.30(95% CI:12.50~24.00),阴性似然比(negative likelihood ratio, LR-)为0.21(95% CI:0.17~0.27),诊断比值比(diagnostic odds ratio,DOR)为82.00(95% CI:51.00~130.00),汇总受试者工作特征(summary receiver operating characteristic, SROC)曲线下面积(area under curve, AUC)为0.95(95% CI:0.93~0.97)[129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206,207,208,209,210,211,212,213,214,215]。一项纳入6个前瞻性筛查试验的个体病例数据Meta分析,对乳腺X线摄影在具有乳腺癌家族史的高危人群中的筛查诊断准确性进行了评价,结果显示,在高危人群中,乳腺X线摄影筛查的灵敏度为55.00%(95% CI:48.00%~62.00%),特异度为94.00%(95% CI:92.70%~95.30%)[216]

问题11:单独使用乳腺超声筛查效果

推荐意见11.1:对于一般风险人群,推荐单独使用乳腺超声进行筛查(强推荐,GRADE证据分级:低)

推荐意见11.2:对于高风险人群,不推荐单独使用乳腺超声进行筛查(强推荐,GRADE证据分级:低)

推荐说明:本指南证据检索与评价小组于2020年开展了系统评价,与诊断结果和随访结果相比,对单独使用超声进行乳腺癌筛查的诊断准确性进行评价,共纳入28个研究,结果显示:(1)在所有人群中单独使用超声进行筛查(n=972 357,28个研究),22个研究合并的灵敏度为68.80%(95% CI:66.10%~71.40%;6个无法合并的研究灵敏度介于29.40%~100.00%之间),特异度为98.90%(95% CI:98.80%~98.90%;2个无法合并的研究特异度分别为75.00%和57.40%),LR+为19.959(95% CI:8.08~49.31),LR-为0.41(95% CI:0.30~0.56),DOR为53.32(95% CI:20.82~136.50),SROC AUC为0.87(95% CI:0.67~1.00)[149,153,165,190,202,203,209,215,217,218,219,220,221,222,223,224,225,226,227,228,229,230,231,232,233,234,235,236]。证据级别为低质量。(2)在无症状普通人群中单独使用超声进行筛查(n=935 041,12个研究):9个研究合并的灵敏度为70.50%(95% CI:56.40%~81.60%;3个无法合并的研究灵敏度介于30.20%与48.20%之间),特异度为99.00%(95% CI:97.90%~99.50%;2个无法合并的研究特异度分别为75.00%和57.40%),LR+为67.47(95% CI:29.14~156.24),LR-为0.30(95% CI:0.19~0.46),DOR为226.50(95% CI:68.74~746.34),SROC AUC为0.97(95% CI:0.95~0.98)[149,153,165,190,202,203,209,215,233,234,235,236]。证据级别为低质量。

问题12:乳腺X线检查联合乳腺超声筛查效果

推荐意见12.1:对于致密型乳腺的一般风险人群,推荐使用乳腺X线检查联合乳腺超声进行筛查(强推荐,GRADE证据分级:中)

推荐意见12.2:对于高风险人群,推荐使用乳腺X线检查联合乳腺超声进行筛查(强推荐,GRADE证据分级:中)

推荐说明:本指南证据检索与评价小组于2020年开展了系统评价,与诊断结果和随访结果相比,使用超声联合乳腺X线检查进行乳腺癌筛查的诊断准确性进行评价,共纳入26个研究,结果显示:(1)在致密乳腺人群中使用乳腺X线检查联合乳腺超声进行筛查(n=142 796,17个研究):15个研究合并的灵敏度为96.20%(95% CI:89.70%~98.60%;1个无法合并的研究灵敏度为90.60%),特异度为92.60%(95% CI:87.50%~95.80%;1个无法合并的研究特异度为96%),LR+为13.05(95% CI:7.58~22.45),LR-为0.04(95% CI:0.02~0.14),DOR为315.30(95% CI:98.12~1013.19),SROC AUC为0.98(95% CI:0.97~0.99)[219,237,238,239,240,241,242,243,244,245,246,247,248,249,250,251,252]。证据级别为中等质量。(2)在高风险人群中使用超声联合乳腺X线检查进行筛查(n=161 057,26个研究):22个研究合并的灵敏度为93.20%(95% CI:85.40%~97.00%;3个无法合并研究的灵敏度介于44%~100%之间),特异度为92.80%(95% CI:88.20%~95.70%;1个无法合并的研究特异度为96%),LR+为13.01(95% CI:7.81~21.67),LR-为0.07(95% CI:0.03~0.16),DOR为177.99(95% CI:64.49~491.23),SROC AUC为0.98(95% CI:0.96~0.99)[219,223,224,225,227,237,238,239,240,241,242,243,244,245,246,247,248,249,250,251,252,253,254,255,256,257]。证据级别为中等质量。本次系统评价结果显示,超声联合乳腺X线检查无论在致密型乳腺人群还是高危人群中均有较好的诊断准确性,综合考虑卫生经济学和筛查实际情况,推荐高风险人群和致密型乳腺人群使用乳腺X线检查联合乳腺超声进行乳腺癌筛查,一般风险人群在经济能力较好地区可考虑使用乳腺X线检查联合乳腺超声进行乳腺癌筛查。

问题13:单独使用乳腺核磁筛查效果

推荐意见13.1:对于一般风险人群,不推荐使用乳腺核磁筛查为常规筛查(强推荐,GRADE证据分级:中)

推荐意见13.2:对于BRCA1/2基因突变携带者,可考虑使用乳腺核磁筛查,但不推荐作为筛查的首选方法(强推荐,GRADE证据分级:中)

推荐说明:本指南证据检索与评价小组于2020年开展了系统评价,以活检或随访作为金标准,对核磁筛查乳腺癌的诊断准确性进行评价,共纳入25个研究,结果显示:(1)在所有人群中单独使用乳腺核磁进行筛查(n=29 192,25个研究):13个研究合并的灵敏度为82.30%(95% CI:71.10%~89.80%;12个无法合并研究的灵敏度介于71%~100%),13个研究合并的特异度为92.20%(95% CI:87.70%~95.20%;5个无法合并研究的特异度介于81.00%~93.60%),LR+为110.60(95% CI:6.63~16.96),LR-为0.19(95% CI:0.11~0.32),DOR为52.21(95% CI:25.54~119.36),SROC AUC为0.94(95% CI:0.92~0.96)[173,223,224,229,230,231,253,258,259,260,261,262,263,264,265,266,267,268,269,270,271,272,273,274,275]。证据级别为中等质量。(2)在BRCA1/2基因突变携带者中单独使用乳腺核磁进行筛查(n=10 955,11个研究):7个研究合并的灵敏度为78.30%(95% CI:66.70%~86.70%;4个无法合并研究的灵敏度介于71.00%~93.80%);7个研究合并的特异度为93.80%(95% CI:91.10%~95.70%;2个无法合并研究的特异度为90.0%和93.60%),LR+为12.65(95% CI:8.78~18.21),LR-为0.23(95% CI:0.15~0.37),DOR为54.61(95% CI:28.76~103.70),SROC AUC为0.94(95% CI:0.92~0.96)[224,229,259,260,261,264,265,268,270,271,275]。证据级别为中等质量。目前,乳腺核磁筛查的敏感度和特异度在所有单独筛查措施中较高,但综合考虑核磁检查费用、检查时长和设备普及率等原因,并不将乳腺核磁作为乳腺癌人群筛查的首要推荐。对于BRCA1/2基因突变携带者,可结合筛查地区经济能力考虑使用乳腺核磁进行筛查。

(六)筛查组织与管理随访

问题14:乳腺癌筛查组织流程

建议乳腺癌筛查的流程参考图2,主要包括签署知情同意书、问卷调查(附件B)、风险评估、筛查技术选择和结果管理与随访

点击查看大图
图2
乳腺癌筛查流程图

注:BI-RADS:乳腺影像报告及数据系统

图2
乳腺癌筛查流程图

问题15:知情同意书的签署

推荐意见15.1:建议所有参加筛查者在自愿的原则下签署知情同意书

推荐意见15.2:建议知情同意书的内容至少包括筛查目的、意义、过程、参加筛查可能获得的益处和风险、筛查费用、保密原则和自愿原则、签字及日期

推荐说明:知情同意能确保筛查对象在筛查过程中获得合理及有效的医疗支持,能帮助筛查对象和医院及医师之间建立良好的信任[276]。我国在2019年发布的大型人群队列研究数据安全技术规范中提到,数据采集人员应向研究对象提供其接受调查必需的所有信息,通过完整充分的说明和介绍,对筛查对象的有关询问进行全面必要的回答和解释,使筛查对象全面了解调查内容及隐私数据安全性保证[277]。因此,本指南建议在乳腺癌筛查之前要签署知情同意书,明确乳腺癌筛查的目的、意义、过程、参加筛查可能获得的益处和风险、筛查费用,并解释说明筛查的保密原则和自愿原则。

问题16:筛查结果管理与随访流程

推荐意见:可参考《中国抗癌协会乳腺癌诊治指南与规范(2019年版)》、国家癌症中心2018年发布的《中国乳腺癌筛查与早诊早治指南》以及ACR制定的被国际广泛采用的乳腺影像报告及数据系统(breast imaging reporting and data system, BI-RADS),对影像诊断结果进行记录、分析[11,12,93]

推荐说明:(1)对于BI-RADS 1类和BI-RADS 2类:无需特殊处理;(2)对于BI-RADS 3类:乳腺X线检查评估为3类病灶,建议在此后6个月时对病灶侧乳腺进行乳腺X线检查复查,第12个月与24个月时对双侧乳腺进行乳腺X线检查复查。如果病灶保持稳定,则可继续随诊;2~3年随访无变化者可以降为BI-RADS 2类;如果随诊过程中病灶消失或缩小,可直接评估为BI-RADS 2类或BI-RADS 1类;若随诊过程中病灶有可疑发现,应考虑活检。超声评估为BI-RADS 3类病灶,建议3~6个月时行超声随访复查,2年随访无变化者可以降为BI-RADS 2类;(3)对于BI-RADS 4a类:可进一步影像检查,必要时活检;(4)对于BI-RADS 4b类:可进一步影像检查,可进行活检;(5)对于BI-RADS 4c类和BI-RADS 5类:可进行活检;(6)对于单项影像学检查(乳腺X线检查或超声)评估为BI-RADS 0类:建议加做其他影像学检查进行联合诊断。例如:致密性乳腺女性的乳腺X线检查结果,当发现不确定病灶时,归为BI-RADS 0类时,有必要补充乳腺超声检查。

四、总结

本指南聚焦于我国40岁及以上女性乳腺癌筛查,是由多学科背景的专家团队,按照国内外公认的规范和方法制定,适用于各级医院恶性肿瘤筛查的医务工作者。与其他已发表的相关指南相比,本指南工作组通过临床问题调研、证据收集与评价、制定专家共识等过程,最终形成了基于证据、平衡获益与风险、综合考虑筛查者意愿、卫生经济学与专家经验的临床问题推荐意见,是循证医学应用于临床实践的代表性指南。本指南对于规范我国现阶段乳腺癌筛查具有切实的指导意义,预期可降低乳腺癌死亡率,提升群体筛查获益,并最终达到降低恶性肿瘤治疗成本,提升社会经济效益,提高恶性肿瘤筛查服务的均质化和同质化目标。

但是,本指南存在局限性。首先,我国暂缺关于乳腺癌筛查的高质量人群随机对照试验,本土高质量证据相对缺乏,基于国外证据得出推荐意见需考虑我国女性乳腺癌发病特征和我国国情;第二,原始研究对人群危险因素合并情况等信息描述不足,导致对于部分问题无法进一步细化推荐意见,或依托专家意见形成推荐意见;第三,筛查的诸多问题暂缺卫生经济学证据,本指南未进一步细化对我国不同经济发展地区的推荐意见。全国各医疗机构在使用本指南进行乳腺癌筛查的实践过程中仍然会存在差异,指南制定工作组也将关注后效评价,在指南更新时改进这些问题。

指南制定顾问组 赫捷(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、郝希山(天津医科大学肿瘤医院)、沈洪兵(南京医科大学)、沈镇宙(复旦大学附属肿瘤医院)、宋尔卫(中山大学孙逸仙纪念医院)

指南制定专家组组长 陈万青(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、李霓(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院);副组长:庞达(哈尔滨医科大学附属第三医院)

指南制定专家组(按姓氏汉语拼音字母排序) 步宏(四川大学华西医院)、陈可欣(天津医科大学肿瘤医院)、陈万青(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、崔久嵬(吉林大学附属第一医院)、付丽(天津医科大学肿瘤医院)、韩优莉(首都医科大学)、何建军(西安交通大学第一附属医院)、贺宇彤(河北医科大学第四医院)、胡志斌(南京医科大学)、黄建(浙江大学第二附属医院)、金锋(中国医科大学附属第一医院)、李静(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、李霓(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、刘东戈(北京医院)、刘运泳(辽宁省肿瘤医院)、马斌林(新疆肿瘤医院)、马飞(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、欧阳取长(湖南省肿瘤医院内科)、庞达(哈尔滨医科大学附属第三医院)、邵志敏(复旦大学附属肿瘤医院)、宋冰冰(黑龙江省癌症中心)、宋张骏(陕西省人民医院)、孙强(北京协和医院)、田捷(中国科学院自动化研究所)、田金徽(兰州大学)、王建东(解放军总医院)、王靖(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、王树森(中山大学附属肿瘤医院)、王翔(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、王勇(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、吴永忠(重庆医科大学附属肿瘤医院)、徐兵河(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、杨碎胜(甘肃省肿瘤医院)、张钢龄(包头市肿瘤医院)、张瑾(天津医科大学肿瘤医院)、曾强(解放军总医院)、周宝森(中国医科大学)、庄贵华(西安交通大学)、邹德宏(浙江省肿瘤医院)

指南制定方法学专家 李江(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、田金徽(兰州大学)、周宝森(中国医科大学)

指南制定工作组名单(按姓氏汉语拼音字母排序) 包蔚郁(甘肃省肿瘤医院)、陈武臻(浙江大学第二附属医院)、杜灵彬(浙江省肿瘤医院)、谷峰(天津医科大学肿瘤医院)、郭兰伟(河南省肿瘤医院)、韩洁(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、韩旭(包头市肿瘤医院)、何淑蓉(北京医院)、洪若熙(中山大学附属肿瘤医院)、黄育北(天津医科大学肿瘤医院)、兰波(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、李鸿涛(新疆医科大学附属肿瘤医院)、李江(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、李俊杰(复旦大学附属肿瘤医院)、李永峰(浙江省肿瘤医院)、梁迪(河北医科大学第四医院)、刘晶晶(天津医科大学肿瘤医院)、刘振宇(中国科学院自动化研究所)、吕章艳(天津医科大学肿瘤医院)、吕铮(吉林大学第一医院)、马红霞(南京医科大学)、欧蕾(解放军总医院)、乔良(四川省肿瘤医院)、沈国双(青海大学附属医院)、沈明望(西安交通大学)、沈松杰(北京协和医院)、田璨(湖南省肿瘤医院)、王虎霞(陕西省肿瘤医院)、王乐(浙江省肿瘤医院)、王昕(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、王仲照(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、魏兵(四川大学华西医院)、吴妮娜(首都医科大学)、吴双伶(中国医科大学附属第一医院)、许建国(兰州大学)、颜仕鹏(湖南省肿瘤医院)、张慧敏(西安交通大学附属第一医院)、张韶凯(河南省肿瘤医院)、张显玉(哈尔滨医科大学附属第三医院)、曾晓华(重庆大学附属肿瘤医院)、郑亚迪(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)

主要执笔团队 陈万青(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、李霓(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、李江(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、田金徽(兰州大学)、郑亚迪(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、刘运泳(辽宁省肿瘤医院)、宋冰冰(黑龙江省癌症中心)、王乐(浙江省肿瘤医院)、颜仕鹏(湖南省肿瘤医院)、周宝森(中国医科大学)、胡志斌(南京医科大学)、吴峥(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、李贺(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、孙殿钦(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、曹毛毛(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、何思怡(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)、杨卓煜(国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院)

本指南制定受国家卫生健康委员会疾病预防控制局委托与指导

志      谢

志谢 指南制定工作组感谢以下专家在本指南制定过程中提出的宝贵建议(按姓氏汉语拼音字母排序) 曹骥、曹素梅、董栋、董华、樊永祥、龚继勇、何美、黄立敏、黄焰、姜晶、姜文珍、雷林、李博、罗鹏飞、马洁、彭绩、史纪元、宋述名、孙喜斌、魏葆珺、魏东华、魏清风、王飞、王慜杰、王宁、王亚希、席云峰、许永杰、严俊、杨莉、于连政、张敏、张永贞、周金意、朱陈

利益冲突

利益冲突 所有作者声明不存在利益冲突

附件A
A.1 中文检索策略
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图A.1
中文检索策略
图A.1
中文检索策略
A.2 英文检索策略
点击查看大图
图A.2
英文检索策略
图A.2
英文检索策略
A.3 文献筛选流程图
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图A.3
文献筛选流程图
图A.3
文献筛选流程图
附录B
乳腺癌风险评估问卷

以下为乳腺癌风险评估可参考内容。

姓名:__________

出生日期:_______年______月_______日(请填写阳历生日)

籍贯:________省______市_______县(区)

民族:1.汉族 2.蒙古族 3.回族 4.满族 5.壮族 6.维吾尔族 7.哈萨克族 8.其他,请注明________

身份证号:_______________________________

本人联系电话:___________________(手机);_______________________(座机)

联系人1电话:____________________(手机);联系人2电话:____________________(手机)

常住地址:_______________________________ ;工作单位:_______________________________

点击查看表格
1.生理和生育情况
1.1您的首次月经年龄是(周岁)?
1.2您是否已绝闭经? 0.否 1.是
1.2.1若是,停经年龄(周岁)
1.3您是否使用激素替代治疗?0.否 1.是,仅雌激素(如更宝芬、补佳乐、协坤、维尼安、更乐、倍美力、得美素、欧适可、松奇、康美华、尼尔雌醇等) 2.是,雌孕激素联合(如诺康律、诺更宁、克龄蒙、倍美安、倍美盈等)
1.3.1若是,使用月数
1.4您是否有活产史? 0.否(未生育、流产、死胎均包括) 1.是
1.4.1若是,初次活产年龄(周岁)
1.5您是否有哺乳史? 0.否 1.是
1.5.1若是,累计哺乳月数(不足1个月按1个月计)
2.乳腺相关疾病史
2.1您是否曾有乳腺活检史或乳腺良性疾病手术史? 0.否 1.是
2.1.1若是,请注明次数
2.2您是否曾进行过BRCA基因检测,结果显示携带有BRCA1/2基因致病性遗传突变 0.否 1.是
2.3您是否曾进行过乳腺X线检查,显示为乳腺实质(或乳房密度)类型为不均匀致密型或致密型 0.否 1.是
3.乳腺癌家族史
3.1您是否有一级亲属(母亲、姐妹及女儿)曾患乳腺癌? 0.否 1.是
3.2您是否有一级亲属(母亲、姐妹及女儿)曾患卵巢癌?  0.否 1.是
3.3您是否有二级亲属(祖母、外祖母及姑姨)50岁前曾患乳腺癌? 0.否 1.是
3.3.1若是,请注明人数
3.4您是否有二级亲属(祖母、外祖母及姑姨)50岁前曾患卵巢癌? 0.否 1.是
3.4.1若是,请注明人数
填写人签字:______________________________填写日期:______________________________
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