中国乳腺癌相关心脏病诊疗共识（2022年版）

doi:10.19401/j.cnki.1007-3639.2022.10.010

中国癌症杂志 ›› 2022, Vol. 32 ›› Issue (10): 1016-1036.doi: 10.19401/j.cnki.1007-3639.2022.10.010

• 指南与共识 • 上一篇

中国乳腺癌相关心脏病诊疗共识（2022年版）

沈赞¹, 邵志敏², 中华医学会肿瘤学分会肿瘤支持康复治疗学组, 中国乳腺癌相关心脏病诊疗共识编写委员会

1. 上海交通大学附属第六人民医院肿瘤内科，上海 200233
2. 复旦大学附属肿瘤医院乳腺外科，上海 200032

收稿日期:2022-08-15 修回日期:2022-09-04 出版日期:2022-10-30 发布日期:2022-11-29
作者简介:沈赞（ORCID: 0000-0002-7934-4396），主任医师，上海市第六人民医院肿瘤内科行政主任，E-mail:sshenzzan@vip.sina.com香港大学肿瘤学博士，主任医师，上海交通大学博士研究生导师。现任上海交通大学附属第六人民医院肿瘤内科行政主任。担任中华医学会肿瘤分会委员兼肿瘤支持康复治疗学组组长、国家卫健委骨软组织肿瘤合理化用药专家组常委兼秘书、中国医药教育协会疑难肿瘤专委会主任委员、中国宋庆龄基金会肿瘤产学研医联体常务副理事长、擅长乳腺癌内科治疗、骨转移癌及骨和软组织肉瘤的诊治。以第一作者和通信作者身份在SCI收录期刊上发表论文61篇，总影响因子150.7分。作为项目负责人主持国家重点研发专项1项、国家自然科学基金面上项目4项。2008年获上海市高级归国人才计划“浦江人才计划”资助。

Chinese consensus of cardio-oncology in breast cancer

SHEN Zan¹, SHAO Zhimin², Cancer Support Rehabilitation Therapy Group of Chinese Medical Association Oncology Branch, the Drafting Committee of China Breast Cancer Related Heart Disease Diagnosis and Treatment Consensus

1. Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200233, China
2. Department of Breast Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

Received:2022-08-15 Revised:2022-09-04 Published:2022-10-30 Online:2022-11-29

摘要/Abstract

摘要：

乳腺癌和心血管疾病是现代社会的两大“杀手”，严重威胁着中国女性的健康，目前两个学科之间关联共性尚未引起临床医师足够的重视，为相关的跨学科合作实践带来一定困难。因此，对于那些已存在心血管系统疾病或心血管疾病风险的乳腺癌患者，临床医师在进行相关抗肿瘤诊疗时，应用类似乳腺癌干预策略的方法来综合评估相关风险，进行相关心脏毒性的预防及治疗干预。目前不少发达国家，已经建立了肿瘤心脏病专科门诊、病房和对应的多学科治疗团队（multidisciplinary treatment teams，MDT）。而在国内，相关学科发展才刚刚开始。可以预见的是，随着乳腺癌检测和治疗手段的不断进步，会有越来越多的乳腺癌患者获得长期的生存，这意味着其中部分患者必然要面临抗肿瘤治疗相关心脏毒性所带来的并发症的风险。因此，一份具有强有力循证医学证据支持的相关指南和临床共识能够为临床医师提供针对性的随访、监测、治疗流程和有效的管理手段，具有十分重要的临床指导意义。本共识旨在指导临床医师对乳腺癌患者进行相关抗肿瘤治疗（化疗、靶向治疗、手术、内分泌治疗、免疫治疗及放疗）的前提下，将心脏保护作为一个整体进行评估和监测，根据监测的结果决定后续干预手段，并决定是否及何时由心脏科医师进行专业会诊，避免因对乳腺癌相关心脏毒性认识不够，导致治疗不及时产生相关不良后果，为中国乳腺癌心脏病诊疗防治提供一份切实可行的临床实践操作流程，最终为改善中国乳腺癌患者的预后作出贡献。

关键词: 乳腺癌, 肿瘤心脏病学, 预防, 治疗

Abstract:

Recent advances in the medical oncological treatment options for cancer have led to a clear improvement in the survival rate worldwide; however, many of the recently developed new drugs are directly or indirectly associated with cardiovascular side effects. Cardiovascular diseases are already the most frequent non-cancerous cause of death in tumor patients. Prevention and early detection of these complications, correct management and timely initiation of specific cardiac medical treatment are the keys to improvement of the cardiovascular prognosis. At present, many developed countries have established oncology-cardiology specialist clinics, wards and related multidisciplinary teams (MDT). In our country, development of cardio-oncology has just on the way. With improvement of survival of breast cancer patients, it is reasonable to foresee that more and more breast cancer patients might suffer from cardiovascular disease, which indicates that it is necessary to focus on risk associated with antitumor therapy-related cardiotoxicity. Therefore, an elaborate guideline supported by solid medical evidence is strongly needed for clinicians major in oncology. This consensus provides an overview and comprehensive summary of the possible cardiotoxic side effects of important oncological therapies and offers possible practical strategies with respect to risk stratification, cardiological follow-up care and management approaches for chemotherapy-induced left ventricular dysfunction. We believe this consensus will provide a practical clinical procedures for treatment and prevention of cardio-oncology in breast cancer in China, and make contributions to improvement of outcome of cardiotoxicity in Chinese breast cancer patients.

Key words: Breast cancer, Cardio-oncology, Prevention, Treatment

中图分类号:

R737.9

沈赞, 邵志敏, 中华医学会肿瘤学分会肿瘤支持康复治疗学组, 中国乳腺癌相关心脏病诊疗共识编写委员会. 中国乳腺癌相关心脏病诊疗共识（2022年版）[J]. 中国癌症杂志, 2022, 32(10): 1016-1036.

SHEN Zan, SHAO Zhimin, Cancer Support Rehabilitation Therapy Group of Chinese Medical Association Oncology Branch, the Drafting Committee of China Breast Cancer Related Heart Disease Diagnosis and Treatment Consensus. Chinese consensus of cardio-oncology in breast cancer[J]. China Oncology, 2022, 32(10): 1016-1036.

图/表 13

图1

表1

乳腺癌常规化疗药物及心脏毒性防治管理（强烈推荐）"

药物名称	心脏毒性	症状管理
蒽环类	左心室功能障碍	① 识别危险因素，包括既往可能发生心脏毒性药物的使用（多柔比星累积剂量>450 mg/m²，表柔比星累积剂量>900 mg/m²）、年龄（<18岁，>65岁）、肝肾功能不全、既往肿瘤治疗史、既往心血管病史 ② 先蒽环后紫杉，分开输注。如先用紫杉类药物，将会降低蒽环类药物的清除率，可能增加心脏毒性 ③ 高危患者或低危患者，但预计阿霉素累积剂量>250 ~ 300 mg/m²（或等量的结构类似物）可使用心脏保护剂右雷佐生/右丙亚胺，且不会显著降低治疗乳腺癌患者的总生存率或无进展生存率 ④ 使用脂质体包裹的阿霉素：心脏毒性发生率降低，但仍具有心脏毒性风险 ⑤ 无症状心功能异常：可考虑给予ACEI/ARB、β-受体阻滞剂治疗，但目前缺少大规模临床研究证据 ⑥ 症状性心衰：需按照最新的中国心力衰竭诊断和治疗指南开展治疗。病情稳定后，是否继续原方案治疗，需综合考虑左室功能异常的严重程度、临床心衰状态、肿瘤预后以及抗肿瘤治疗的效果
紫杉醇	左心室功能障碍，心肌缺，QTc间期延长，心动过缓	① 具有高危因素者可考虑使用脂质体包裹的紫杉醇，但仍具有一定心脏毒性风险。白蛋白结合型紫杉醇的心脏风险可能稍高或类似于溶剂型紫杉醇，这取决于白蛋白结合型紫杉醇的用量 ② 无症状心功能异常的管理同蒽环类心脏毒性管理 ③ 症状性心衰：同蒽环类药物心脏毒性管理6 ④ 心肌缺血：临床表现个体化差异明显，可采取心肌缺血的标准处理流程 ⑤ QT间期延长：纠正诱发因素，纠正电解质异常，控制QT间期延长的心血管病危险因素；QTc间期正常后可从小剂量开始继续化疗 ⑥ 心动过缓：积极治疗原发疾病，必要时考虑停药，或联系专科医师行起搏器植入
多西他赛	左心室功能障碍，心肌缺血	同紫杉醇疾病管理②、③、④
环磷酰胺	左心室功能障碍	左心室功能障碍的处理同紫杉醇疾病管理②、③
5-氟尿嘧啶	心肌缺血	① 可选用雷替曲塞代替 ② 心肌缺血的处理同紫杉醇④
卡培他滨	心肌缺血	① 可选用雷替曲塞代替 ② 心肌缺血的处理同紫杉醇疾病管理④
顺铂	静脉血栓栓塞	① 停药；②遵照相关抗凝指南建议执行
艾立布林	CHF，缓慢性心律失常先天性长QT综合征加重	① 纠正低钾/低镁血症 ② 避免与其他延长QT间期的药物共同给药，可能会引起累加效应（例如，Ⅰa或Ⅲ类抗心律失常药）

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药物名称	常用剂量	心脏毒性
曲妥珠单抗	周方案：初始负荷剂量4 mg/kg；维持剂量2 mg/kg； 3周方案：初始8 mg/kg之后6 mg/kg	左心室功能不全，心律失常，心力衰竭，心肌病
帕妥珠单抗	3周方案：初始840 mg；之后420 mg	左心室功能不全；罕见左心功能衰竭
拉帕替尼	1 250 mg qd	心脏毒性的总发生率约为2.7%，多表现为射血分数下降
来那替尼	240 mg/qd	无症状性左室射血分数下降
吡咯替尼	400 mg/qd	可能导致QT间期延长或LVEF下降
抗体偶联药物 (TDM-1)	3周方案： 3.6 mg/kg	心脏毒性的总体发生率为 3.37%，包括射血分数下降，心肌缺血及心律失常，多为可逆性
CDK 4/6抑制剂	阿贝西利（100 mg bid 或150 mg bid) 哌柏西利（125 mg qd，d 21，休息7天）瑞博西尼（600 mg qd，d 21，休息7天）	与内分泌治疗联合时，增加静脉血栓栓塞的风险；瑞博西尼可能引起剂量依赖性QTc延长

药物名称	常用剂量	心脏毒性	症状管理
阿替利珠单抗	840 mg, d1 d15 q4w	心肌炎	监测+激素+其他治疗措施
帕博利珠单抗	200 mg, q3W×4	心肌炎	监测+激素+其他治疗措施
卡瑞利珠单抗	200 mg, d1 d15 q4w	心肌炎	监测+激素+其他治疗措施

药物名称	常用剂量	对血脂效应	症状管理
他莫昔芬	20 mg/d	TC ↓，LDL-C↓，HDL-C↑或↓或-，TG ↑或-	积极血脂监测
托瑞米芬	40 mg/d	TC ↓，LDL-C↓，HDL-C↑，TG ↓或-	积极血脂监测
非甾体类芳香化酶抑制剂	来曲唑：2.5 mg/d；阿那曲唑：1 mg/d	TC ↑，LDL-C↑，HDL-C↑或-，TG ↑或-	积极血脂监测
甾体类芳香化酶抑制剂	依西美坦：25 mg/d	TC -或轻度↑或↓，LDL-C↑或↓或-，HDL-C↑或↓或-，TG↑或↓或--	积极血脂监测
氟维司群	500 mg q21d	TC ↓，LDL-C↓	积极血脂监测
促性腺激素释放激素激动剂	亮丙瑞林3.75 mg q28d戈舍瑞林 3.6 mg q28d	TC ↑，LDL-C-或↑，HDL-C↑，TG ↑或-	积极血脂监测

适用人群	接受乳腺或胸壁±内乳区放疗的患者；
观察终点	主要冠状动脉事件（心肌梗死，冠状动脉血运重建，或死于缺血性心脏病）
数量关系	平均心脏剂量（MHD）每增加1 Gy，主要冠状动脉事件发生率线性增加7.4%
零级预防（参照心血管疾病的零级预防、一级预防、二级预防的表述）	充分评估患者情况（根据指南决定是否可减免放疗?若符合低危乳腺癌特征，是否可考虑部分乳腺放疗?区域淋巴引流区预防放疗是否可减免内乳区照射?）
Ⅰ级预防（放疗计划与实施阶段，以降低MHD为目标）	① 体位固定：侧卧位或俯卧位，适合大乳房或乳房下垂，仅需要乳房放疗；② 模拟定位：首选CT模拟定位；③ 呼吸控制技术：仰卧位时采用深吸气屏气（DIBH），呼吸门控；④ 放疗计划：三维适形放疗或调强放疗（IMRT或VMAT）技术；⑤ 治疗实施：图像引导的放疗提高精度；光子放疗的替代治疗技术：质子治疗
Ⅱ级预防	早期发现RIHD，及早干预

麻醉剂名称	剂量	心脏效应	症状管理
七氟烷	麻醉诱导阶段浓度：2.5%~4.0%（与50%~70%氧化亚氮吸入）；麻醉维持阶段浓度：常为4.0%以下	减轻化疗药物导致的心肌细胞损伤，术中起保护心肌的作用^*	术前ECG，监测cTnI、BNP或NT-proBNP；术中密切监护
丙泊酚	麻醉诱导阶段：1.5~2.5 mg/kg体重，于30~45 s注完；麻醉维持阶段：4~12 mg/(kg·h)	减轻化疗药物导致的心肌损伤，抑制心肌细胞凋亡^*	术前ECG，监测cTnI、BNP或NT-proBNP；术中密切监护

中国乳腺癌相关心脏病诊疗共识（2022年版）

Chinese consensus of cardio-oncology in breast cancer

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