中国乳腺癌患者BRCA1/2基因检测与临床应用专家共识（2025年版）

doi:10.19401/j.cnki.1007-3639.2025.07.010

摘要/Abstract

摘要：

乳腺癌是中国女性常见的恶性肿瘤之一，其中遗传性乳腺癌占5%~10%，BRCA1/2基因突变是最主要的遗传易感因素。近年来，尽管多腺苷二磷酸核糖聚合酶[poly (ADP-ribose) polymerase，PARP]抑制剂等靶向药物的应用改善了BRCA突变乳腺癌患者的预后，但在临床实践中仍存在诸多亟待解决的问题，包括突变检测的规范化、精准治疗策略的优化及长期管理的完善等。针对这些临床问题，本共识专家组基于《中国乳腺癌患者BRCA1/2基因检测与临床应用专家共识（2018年版）》及国内外最新循证医学证据，结合中国临床实践特点，对BRCA1/2基因检测的适用人群、检测方法、结果解读、治疗策略和风险管理等关键环节进行了系统评估和深入讨论，最终形成《中国乳腺癌患者BRCA1/2基因检测与临床应用专家共识（2025年版）》。主要更新内容包括：① 增加BRCA1/2基因突变与程序性死亡蛋白配体-1（programmed death ligand-1，PD-L1）表达的关系，以及BRCAness类型的相关内容；② 规范基因检测的应用，如增加临床检测的意义、时机及样本选择、优化BRCA检测人群；③ 更新治疗策略，如BRCA1/2基因突变的非药物治疗、BRCA1/2基因突变三阴性乳腺癌（triple-negative breast cancer，TNBC）患者的治疗、BRCA1/2基因突变激素受体（hormone receptor，HR）⁺/人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）^-乳腺癌患者的治疗决策、PARP抑制剂的临床使用及不良反应管理；④ 增加长期风险管理的相关内容，如涵盖随访管理、预防性手术指征、新增基因检测的质量控制与要求、更新基因检测流程、报告内容及解读等。本共识旨在为临床医师提供规范化的诊疗指导，推动BRCA基因突变乳腺癌的精准医疗发展，最终改善患者生存及预后。随着研究的深入，本共识今后将持续更新以纳入最新的循证医学证据。本共识已在国际实践指南注册平台（Practice guideline REgistration for transPAREncy，PREPARE）注册，注册号为PREPARE-2025CN1085。

关键词: 乳腺癌, BRCA1/2基因, 治疗, 预防, 检测, 共识

Abstract:

Breast cancer remains one of the frequently diagnosed malignant tumors among Chinese women, with hereditary cases accounting for 5%-10% of all diagnoses, where BRCA1/2 gene mutations serve as the primary genetic predisposition factors. Although targeted therapies like poly (ADP-ribose) polymerase (PARP) inhibitors have significantly improved prognoses for patients with BRCA-mutated breast cancer in recent years, critical clinical challenges persist, including the standardization of genetic testing protocols, optimization of precision treatment approaches, and refinement of long-term management strategies. In response to these challenges, our expert panel has conducted a comprehensive update to the 2018 Edition of this consensus by integrating the latest global evidence-based medical research with China’s unique clinical practice characteristics. This 2025 Edition provides systematic evaluations and recommendations on five key aspects: indications for BRCA1/2 gene testing, testing methodologies, result interpretation, treatment strategies, and risk management. The main updates include: ① Increasing the relationship between BRCA1/2 gene mutations and programmed death ligand-1 (PD-L1) expression, as well as related content on BRCAness types; ② Standardizing the application of genetic testing, such as increasing the significance, timing, and sample selection of clinical testing, and optimizing the BRCA testing population; ③ Updating treatment strategies, such as non-drug treatment of BRCA1/2 gene mutation, treatment of triple negative breast cancer (TNBC) patients with BRCA1/2 gene mutation, treatment decisions of hormone receptor (HR)⁺/human epidermal growth factor receptor 2 (HER2)^- breast cancer patients with BRCA1/2 gene mutation, clinical use of PARP inhibitors and adverse reaction management; ④ Addion of relevant content on long-term risk management, such as covering follow-up management, indications for preventive surgery, quality control and requirements for new genetic testing, updating genetic testing processes, report content and interpretation. This consensus aimed to establish standardized diagnostic and therapeutic frameworks for clinicians, advance precision medicine in BRCA-mutated breast cancer, and ultimately improve patient survival outcomes. As new evidence emerges, continuous updates will be implemented to incorporate the latest research findings. This consensus has been registered on the Practice guideline REgistration for transPAREncy (PREPARE) platform (registration number: PREPARE-2025CN1085).

Key words: Breast cancer, BRCA1/2 gene, Therapy, Prevention, Detection, Consensus

中图分类号:

R737.9

王红霞, 殷咏梅, 胡夕春. 中国乳腺癌患者BRCA1/2基因检测与临床应用专家共识（2025年版）[J]. 中国癌症杂志, 2025, 35(7): 710-734.

WANG Hongxia, YIN Yongmei, HU Xichun. Expert consensus on BRCA1/2 gene testing and clinical application in Chinese breast cancer patients (2025 edition)[J]. China Oncology, 2025, 35(7): 710-734.

图/表 5

图1

表1

表2

表3

不同BRCA突变阳性携带者人群对应的管理方案"

对应人群	管理方案
女性	⑴ 从18岁开始进行乳房自检，25岁开始定期（6~12个月）乳腺检查。 ⑵ 乳腺筛查：① 如家族中有人在30岁前确诊乳腺癌，25~29岁每年1次乳腺MRI（优先）或乳腺X射线摄影检查；② 30~75岁，每年1次乳腺X射线摄影和乳腺MRI筛查；③ >75岁，视个人情况而定；④ 对于有BRCA突变，接受过乳腺癌治疗的女性但未双侧乳腺患癌，继续对对侧乳腺每年进行乳腺X射线摄影和MRI检查。 ⑶ 考虑能降低风险的乳腺切除手术。咨询应包括关于保护程度的讨论、乳房再造和风险事宜。另外，还应该考虑家族史、对侧乳腺癌的患癌风险及生存预期等。 ⑷ 向已完成生育的35~40岁女性推荐RRSO（需向妇科肿瘤医师咨询决定）。因为携带BRCA2基因突变的卵巢癌患者发病年龄比携带BRCA1基因突变的患者平均晚8~10年，对于已经最大化实现乳腺癌防护（如已进行双侧乳腺切除术）的BRCA2基因突变者将RRSO延至40~45岁进行是合理的。 ⑸ 有限数据表明，携带BRCA1致病性/可能致病性突变的女性患浆液性子宫癌的风险可能略有增加，需要进一步评估BRCA人群患浆液性子宫癌的风险。 ⑹ 进行RRM和（或）RRSO时要综合考虑社会心理、社交和生活质量方面。 ⑺ 对于不选择RRSO的患者，需要从30~35岁开始遵循临床医师的指导进行筛查。如经阴道超声和血清CA125检查，但灵敏度和特异度都不高，不是有效的筛查手段。 ⑻ 可考虑使用降低乳腺癌和卵巢癌风险的药物
男性	⑴ 从35岁开始，学会乳房自检。 ⑵ 从35岁开始，每12个月进行1次临床乳腺检查。 ⑶ 从45岁开始：① 推荐BRCA2携带者进行前列腺癌筛查；② BRCA1携带者可考虑前列腺癌筛查
女性和男性	⑴ 学习癌症相关的，尤其是BRCA基因突变相关的体征和症状； ⑵ 胰腺癌和黑色素瘤没有特异性的筛查指南，但可以根据家族观察来制订个性化筛查方案
亲属	⑴ 告知亲属可能的遗传性癌症风险及其风险评估和管理策略； ⑵ 推荐进行遗传咨询，并考虑对有风险的亲属进行基因检测
育龄人群	⑴ 育龄患者，建议做产前诊断或辅助生殖（包括胚胎植入前遗传诊断），讨论应包含已知风险、局限性和这些技术的优势； ⑵ BRCA2基因突变可能与罕见的常染色体隐性遗传有关。建议突变携带者配偶进行相同基因的潜在携带者测试（基因检测），用以辅助生育决定、风险评估及管理

表3

表4

BRCA基因检测流程及质控要点"

检测流程	质控要求
样本采集、运输及保存	采集：采集时需戴手套，防止病原微生物及采集人员脱落细胞污染；容器应密闭、一次性、无菌、无核酸酶及其他扩增抑制物。运输：血液、唾液、口腔拭子、石蜡包埋组织可常温运输，新鲜组织应置于冰上运输。保存：所有样本可在4 ℃冰箱中短期保存，时间不超过1周；血液或石蜡包埋组织在-20或-80 ℃冰箱中长期保存；新鲜组织在液氮罐或-80 ℃冰箱中长期保存
核酸DNA抽提	主要评估：DNA纯度、浓度及片段化程度。推荐使用：染料法或紫外分光光度法准确计量所得DNA浓度和纯度；琼脂糖凝胶电泳等方法对片段化程度进行评估
文库制备	评估：文库DNA浓度及片段大小。推荐使用：Qubit或实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）测定文库浓度；Bioanalyzer 2100分析片段大小
上机测序	主要评估：下机原始数据的质量。推荐使用：Q30或Q20值>75%；鸟嘌呤-胞嘧啶含量应在45%~60%
数据分析	主要评估：突变丰度、测序深度、覆盖度和均一性。推荐使用：⑴ 突变丰度：胚系突变丰度理论上为50%或100%，而体细胞突变丰度可能很低。 ⑵ 测序深度：基于扩增的最低测序深度，胚系突变应>200×，体细胞突变应>1000×；基于捕获（去冗余后）的最低测序深度，胚系突变应>100×，体细胞突变应>500×。 ⑶ 覆盖度和均一性：目标区域的覆盖率应达100%，深度均一性应不低于90%
突变解读	参考最新的国际、国内关于突变解读的共识和指南。同一突变依据不同指南版本或判断标准所得的致病性分类结果可能略有差异，因此建议在突变分类时具体指明所依据的指南或标准名称。同时应至少2人参与突变解读过程，以便于校验

表4

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评分标准	分数
治疗前临床分期
Ⅰ/ⅡA期	0
ⅡB/ⅢA期	1
ⅢB/ⅢC期	2
术后病理学分期
0/Ⅰ期	0
ⅡA/ⅡB/ⅢA/ⅢB期	1
ⅢC期	2
ER状态
ER⁺	0
ER^-	1
细胞核分级
1-2	0
3	1

检查	推荐建议	缺点
乳腺超声联合乳腺X射线摄影检查	乳腺X射线摄影检查建议从30岁开始，每年1次，或从家族中发现小于25岁的先证者开始；每半年进行1次超声检查，超声检查有问题时建议采用其他影像手段进一步检查	对于BRCA1/2基因突变携带者而言，乳腺X射线摄影检测乳腺癌的灵敏度似乎低于其他高危妇女；对于乳腺腺体致密者，有漏诊风险
乳腺MRI检查	明确有BRCA1/2基因突变携带者的首选检查，25岁开始每年1次（月经期的第7~15天），可以增加乳腺癌和早期病变的检出率，符合多数指南的要求	特异度较低，对有疑问的小结节常需要配合MRI引导下的定位或活检，价格较高