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

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

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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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参考文献 144

[1]	孔令泉, 吴凯南, 厉红元. 乳腺肿瘤心脏病学[M]. 北京: 科学出版社, 2018.
[2]	RAGLE D H, VILLALOBOS D A, LEZAMA F S, et al. Cardio-oncology cardiovascular toxicity and antineoplastics[J]. Cardiovas Metab Sci, 2021, 32(1): 42-55. doi: 10.35366/98230
[3]	PENG J, RUSHTON M, JOHNSON C, et al. An international survey of healthcare providers' knowledge of cardiac complications of cancer treatments[J]. Cardiooncology, 2019, 5: 12. doi: 10.1186/s40959-019-0049-2 pmid: 32154018
[4]	MEHTA L S, WATSON K E, BARAC A, et al. Cardiovascular disease and breast cancer: Where these entities intersect: a scientific statement from the American heart association[J]. Circulation, 2018, 137(8).
[5]	《中国心血管健康与疾病报告》编写组. 《中国心血管健康与疾病报告2021》概述[J]. 中国心血管病研究, 2022, 20(7): 577-596.
	The Writing Committee of China Cardiovascular Health and Disease Report. Key points of report on cardiovascular health and diseases in China 2021[J]. Chin J Cardiovasc Res, 2022, 20(7): 577-596.
[6]	尹周一, 王梦圆, 游伟程, 等. 2022美国癌症统计报告解读及中美癌症流行情况对比[J]. 肿瘤综合治疗电子杂志, 2022, 8(2): 54-63.
	YIN Z Y, WANG M Y, YOU W C, et al. Interpretation on the report of American cancer statistics, 2022 and comparison of cancer prevalence in China and America[J]. J Multidiscip Cancer Manag Electron Version, 2022, 8(2): 54-63.
[7]	刘威, 王黎君, 齐金蕾, 等. 1990—2017年中国女性乳腺癌疾病负担分析[J]. 中华流行病学杂志, 2021(7): 1225-1230.
	LIU W, WANG L J, QI J L, et al. Disease burden of breast cancer in women in China, 1990-2017[J]. Chin J Epidemiol, 2021(7): 1225-1230.
[8]	王乐, 岳馨培, 石菊芳, 等. 我国既往二十年乳腺癌经济负担研究[J]. 中国慢性病预防与控制, 2017, 25(2): 143-146.
	WANG (L /Y), YUE X P, SHI J F, et al. Study on the economic burden of breast cancer in the past 20 years in China[J]. Chin J Prev Control Chronic Dis, 2017, 25(2): 143-146.
[9]	ZHENG R S, ZHANG S W, ZENG H M, et al. Cancer incidence and mortality in China, 2016[J]. J Natl Cancer Cent, 2022, 2(1): 1-9.
[10]	胡崇珠, 杨颖, 方志沂. 中国乳腺癌患者生活质量研究进展[J]. 中华乳腺病杂志(电子版), 2010, 4(6): 666-670.
	HU C Z, YANG Y, FANG Z Y. Research progress on quality of life of breast cancer patients in China[J]. Chin J Breast Dis Electron Ed, 2010, 4(6): 666-670.
[11]	JONES L M, STONER L, BROWN C, et al. Cardiovascular disease among breast cancer survivors: the call for a clinical vascular health toolbox[J]. Breast Cancer Res Treat, 2013, 142(3): 645-653. doi: 10.1007/s10549-013-2766-9
[12]	马飞, 卢雯平, 徐兵河. 乳腺癌全方位全周期健康管理[M]. 上海: 上海科学技术出版社, 2018.
[13]	BRADSHAW P T, STEVENS J, KHANKARI N, et al. Cardiovascular disease mortality among breast cancer survivors[J]. Epidemiology, 2016, 27(1): 6-13. doi: 10.1097/EDE.0000000000000394 pmid: 26414938
[14]	SWAIN S M, WHALEY F S, EWER M S. Congestive heart failure in patients treated with doxorubicin[J]. Cancer, 2003, 97(11): 2869-2879. doi: 10.1002/cncr.11407
[15]	ZHENG P P, LI J, KROS J M. Breakthroughs in modern cancer therapy and elusive cardiotoxicity: critical research-practice gaps, challenges, and insights[J]. Med Res Rev, 2018, 38(1): 325-376. doi: 10.1002/med.21463
[16]	CARDINALE D, IACOPO F, CIPOLLA C M. Cardiotoxicity of anthracyclines[J]. Front Cardiovasc Med, 2020, 7: 26. doi: 10.3389/fcvm.2020.00026 pmid: 32258060
[17]	EVANS J D W, DOBBIN S J H, PETTIT S J, et al. High-sensitivity cardiac troponin and new-onset heart failure: a systematic review and meta-analysis of 67, 063 patients with 4, 165 incident heart failure events[J]. JACC Heart Fail, 2018, 6(3): 187-197. doi: 10.1016/j.jchf.2017.11.003
[18]	VALCOVICI M, ANDRICA F, SERBAN C, et al. Cardiotoxicity of anthracycline therapy: current perspectives[J]. Arch Med Sci, 2016, 12(2): 428-435. doi: 10.5114/aoms.2016.59270 pmid: 27186191
[19]	BALDINI E, PROCHILO T, SALVADORI B, et al. Multicenter randomized phase III trial of epirubicin plus paclitaxel vs epirubicin followed by paclitaxel in metastatic breast cancer patients: focus on cardiac safety[J]. Br J Cancer, 2004, 91(1): 45-49. doi: 10.1038/sj.bjc.6601883
[20]	HEQUET O, LE Q H, MOULLET I, et al. Subclinical late cardiomyopathy after doxorubicin therapy for lymphoma in adults[J]. J Clin Oncol, 2004, 22(10): 1864-1871. pmid: 15143078
[21]	ARMENIAN S H, SUN C L, FRANCISCO L, et al. Late congestive heart failure after hematopoietic cell transplantation[J]. J Clin Oncol, 2008, 26(34): 5537-5543. doi: 10.1200/JCO.2008.17.7428 pmid: 18809605
[22]	BOWLES E J, WELLMAN R, FEIGELSON H S, et al. Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study[J]. J Natl Cancer Inst, 2012, 104(17): 1293-1305. doi: 10.1093/jnci/djs317 pmid: 22949432
[23]	HERRMANN J, LERMAN A, SANDHU N P, et al. Evaluation and management of patients with heart disease and cancer: cardio-oncology[J]. Mayo Clin Proc, 2014, 89(9): 1287-1306. doi: 10.1016/j.mayocp.2014.05.013 pmid: 25192616
[24]	CHOW E J, CHEN Y, KREMER L C, et al. Individual prediction of heart failure among childhood cancer survivors[J]. J Clin Oncol, 2015, 33(5): 394-402. doi: 10.1200/JCO.2014.56.1373 pmid: 25287823
[25]	FLOYD J D, NGUYEN D T, LOBINS R L, et al. Cardiotoxicity of cancer therapy[J]. J Clin Oncol, 2005, 23(30): 7685-7696. pmid: 16234530
[26]	TAN-CHIU E, YOTHERS G, ROMOND E, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31[J]. J Clin Oncol, 2005, 23(31): 7811-7819. pmid: 16258083
[27]	SPEYER J L, GREEN M D, KRAMER E, et al. Protective effect of the bispiperazinedione ICRF-187 against doxorubicin-induced cardiac toxicity in women with advanced breast cancer[J]. N Engl J Med, 1988, 319(12): 745-752. doi: 10.1056/NEJM198809223191203
[28]	VENTURINI M, MICHELOTTI A, DEL MASTRO L, et al. Multicenter randomized controlled clinical trial to evaluate cardioprotection of dexrazoxane versus no cardioprotection in women receiving epirubicin chemotherapy for advanced breast cancer[J]. J Clin Oncol, 1996, 14(12): 3112-3120. pmid: 8955656
[29]	MARTY M, ESPIÉ M, LLOMBART A, et al. Multicenter randomized phase Ⅲ study of the cardioprotective effect of dexrazoxane (cardioxane) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy[J]. Ann Oncol, 2006, 17(4): 614-622. doi: 10.1093/annonc/mdj134
[30]	KIM I H, LEE J E, YOUN H J, et al. Cardioprotective effect of dexrazoxane in patients with HER2-positive breast cancer who receive anthracycline based adjuvant chemotherapy followed by trastuzumab[J]. J Breast Cancer, 2017, 20(1): 82-90. doi: 10.4048/jbc.2017.20.1.82
[31]	HOFHEINZ R D, GNAD-VOGT S U, BEYER U, et al. Liposomal encapsulated anti-cancer drugs[J]. Anticancer Drugs, 2005, 16(7): 691-707. doi: 10.1097/01.cad.0000167902.53039.5a
[32]	OLIVIERI J, PERNA G P, BOCCI C, et al. Modern management of anthracycline-induced cardiotoxicity in lymphoma patients: low occurrence of cardiotoxicity with comprehensive assessment and tailored substitution by nonpegylated liposomal doxorubicin[J]. Oncologist, 2017, 22(4): 422-431. doi: 10.1634/theoncologist.2016-0289 pmid: 28275118
[33]	O'BRIEN M E, WIGLER N, INBAR M, et al. Reduced cardiotoxicity and comparable efficacy in a phase Ⅲ trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer[J]. Ann Oncol, 2004, 15(3): 440-449. doi: 10.1093/annonc/mdh097
[34]	CARDINALE D, COLOMBO A, SANDRI M T, et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition[J]. Circulation, 2006, 114(23): 2474-2481. pmid: 17101852
[35]	中华医学会心血管病学分会心力衰竭学组, 中国医师协会心力衰竭专业委员会, 中华心血管病杂志编辑委员会. 中国心力衰竭诊断和治疗指南2018[J]. 中华心力衰竭和心肌病杂志(中英文), 2018, 2(4): 196-225.
	Heart Failure Group of Cardiology Branch of Chinese Medical Association, Heart Failure Professional Committee of Chinese Medical Doctor Association, Editorial Committee of Chinese Journal of Cardiology. Chinese guidelines for diagnosis and treatment of heart failure 2018 [J] Chin J Heart Failure Cardiomyopathy (Chinese and English), 2018, 2 (4): 196-225.
[36]	HUANG S T, WANG Y P, CHEN Y H, et al. Liposomal paclitaxel induces fewer hematopoietic and cardiovascular complications than bioequivalent doses of Taxol[J]. Int J Oncol, 2018, 53(3): 1105-1117.
[37]	LIU M, LIU S Y, YANG L, et al. Comparison between nab-paclitaxel and solvent-based taxanes as neoadjuvant therapy in breast cancer: a systematic review and meta-analysis[J]. BMC Cancer, 2021, 21(1): 118. doi: 10.1186/s12885-021-07831-7 pmid: 33541289
[38]	KHATIB R, SABIR F R N, OMARI C, et al. Managing drug-induced QT prolongation in clinical practice[J]. Postgrad Med J, 2021, 97(1149): 452-458. doi: 10.1136/postgradmedj-2020-138661 pmid: 33122341
[39]	DEAC A L, BURZ C C, BOCSAN I C, et al. Fluoropyrimidine-induced cardiotoxicity[J]. World J Clin Oncol, 2020, 11(12): 1008-1017. doi: 10.5306/wjco.v11.i12.1008 pmid: 33437663
[40]	KÖHNE C H, THUSS-PATIENCE P, FRIEDRICH M, et al. Raltitrexed (tomudex): an alternative drug for patients with colorectal cancer and 5-fluorouracil associated cardiotoxicity[J]. Br J Cancer, 1998, 77(6): 973-977. doi: 10.1038/bjc.1998.160
[41]	甲磺酸艾立布林注射液说明书.核准日期:2019年07月12日,修订日期:2019年09月18日. 2019, 卫材(中国)药业有限公司.
	Instruction manual of eribrin mesylate injection Approval date: July 12,2019; revision date: September 18, 2019 2019, Eisai (China) Pharmaceutical Co., Ltd
[42]	HUDIS C A. Trastuzumab: mechanism of action and use in clinical practice[J]. N Engl J Med, 2007, 357(1): 39-51. doi: 10.1056/NEJMra043186
[43]	EWER S M, EWER M S. Cardiotoxicity profile of trastuzumab[J]. Drug Saf, 2008, 31(6): 459-467. doi: 10.2165/00002018-200831060-00002
[44]	EWER M S, VOOLETICH M T, DURAND J B, et al. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment[J]. J Clin Oncol, 2005, 23(31): 7820-7826. pmid: 16258084
[45]	PEREZ E A, SUMAN V J, DAVIDSON N E, et al. Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial[J]. J Clin Oncol, 2008, 26(8): 1231-1238. doi: 10.1200/JCO.2007.13.5467 pmid: 18250349
[46]	SENDUR M A, AKSOY S, ALTUNDAG K. Pertuzumab-induced cardiotoxicity: Safety compared with trastuzumab[J]. Future Oncol, 2015, 11(1): 13-15. doi: 10.2217/fon.14.184 pmid: 25572781
[47]	LEES C, YAZDAN-ASHOORI P, JERZAK K J, et al. Takotsubo cardiomyopathy during anti-HER2 therapy for metastatic breast cancer[J]. Oncol, 2019, 24(2): e80-e82. doi: 10.1634/theoncologist.2018-0285
[48]	CHOI H D, CHANG M J. Cardiac toxicities of lapatinib in patients with breast cancer and other HER2-positive cancers: A meta-analysis[J]. Breast Cancer Res Treat, 2017, 166(3): 927-936. doi: 10.1007/s10549-017-4460-9
[49]	GUAN Z Z, XU B H, DESILVIO M L, et al. Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer[J]. J Clin Oncol, 2013, 31(16): 1947-1953. doi: 10.1200/JCO.2011.40.5241 pmid: 23509322
[50]	CHAN A, DELALOGE S, HOLMES F A, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet Oncol, 2016, 17(3): 367-377. doi: S1470-2045(15)00551-3 pmid: 26874901
[51]	PARK J W, LIU M C, YEE D, et al. Adaptive randomization of neratinib in early breast cancer[J]. N Engl J Med, 2016, 375(1): 11-22. doi: 10.1056/NEJMoa1513750
[52]	BURSTEIN H J, SUN Y, DIRIX L Y, et al. Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer[J]. J Clin Oncol, 2010, 28(8): 1301-1307. doi: 10.1200/JCO.2009.25.8707 pmid: 20142587
[53]	XUHONG J C, QI X W, ZHANG Y, et al. Mechanism, safety and efficacy of three tyrosine kinase inhibitors lapatinib, neratinib and pyrotinib in HER2-positive breast cancer[J]. Am J Cancer Res, 2019, 9(10): 2103-2119.
[54]	PONDÉ N, AMEYE L, LAMBERTINI M, et al. Trastuzumab emtansine(T-DM1)-associated cardiotoxicity: pooled analysis in advanced HER2-positive breast cancer[J]. Eur J Cancer, 2020, 126: 65-73. doi: 10.1016/j.ejca.2019.11.023
[55]	THEIN K Z, BALL S, ZAW M H, et al. Updated meta-analysis of randomized controlled trials (RCTs) to determine the CDK 4/6 inhibitors associated venous thromboembolism (VTE) risk in hormone receptor-positive breast cancer (BC) patients[J]. Ann Oncol, 2018, 29: viii606.
[56]	INFANTE J R, CASSIER P A, GERECITANO J F, et al. A phase I study of the cyclin-dependent kinase 4/6 inhibitor ribociclib (LEE011) in patients with advanced solid tumors and lymphomas[J]. Clin Cancer Res, 2016, 22(23): 5696-5705. pmid: 27542767
[57]	BONACA M P, OLENCHOCK B A, SALEM J E, et al. Myocarditis in the setting of cancer therapeutics: proposed case definitions for emerging clinical syndromes in cardio-oncology[J]. Circulation, 2019, 140(2): 80-91. pmid: 31390169
[58]	HU J R, FLORIDO R, LIPSON E J, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors[J]. Cardiovasc Res, 2019, 115(5): 854-868. doi: 10.1093/cvr/cvz026
[59]	SCHMID P, ADAMS S, RUGO H S, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer[J]. N Engl J Med, 2018, 379(22): 2108-2121. doi: 10.1056/NEJMoa1809615
[60]	SCHMID P, CORTES J, PUSZTAI L, et al. Pembrolizumab for early triple-negative breast cancer[J]. N Engl J Med, 2020, 382(9): 810-821. doi: 10.1056/NEJMoa1910549
[61]	THIBAULT C, VANO Y, SOULAT G, et al. Immune checkpoint inhibitors myocarditis: Not all cases are clinically patent[J]. Eur Heart J, 2018, 39(38): 3553. doi: 10.1093/eurheartj/ehy485 pmid: 30107497
[62]	中国抗癌协会整合肿瘤心脏病学分会, 中华医学会心血管病学分会肿瘤心脏病学学组, 中国医师协会心血管内科医师分会肿瘤心脏病学专业委员会, 等. 免疫检查点抑制剂相关心肌炎监测与管理中国专家共识(2020版)[J]. 中国肿瘤临床, 2020, 47(20): 1027-1038.
	Integrated Cancer Cardiology Branch of China Anti Cancer Association, Cancer Cardiology Group of Cardiovascular Branch of Chinese Medical Association, Cancer Cardiology Professional Committee of Cardiovascular Physicians Branch of Chinese Medical Association, et al. Chinese expert consensus on the surveillance and management of immune checkpoint inhibitor-related myocarditis (2020 version)[J]. Cancer Biol Med, 2020, 47(20): 1027-1038.
[63]	THOMPSON J A, SCHNEIDER B J, BRAHMER J, et al. Management of immunotherapy-related toxicities, version 1.2022, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2022, 20(4): 387-405. doi: 10.6004/jnccn.2022.0020
[64]	REID P D, CIFU A S, BASS A R. Management of immunotherapy-related toxicities in patients treated with immune checkpoint inhibitor therapy[J]. JAMA, 2021, 325(5): 482-483. doi: 10.1001/jama.2020.17308 pmid: 33528524
[65]	中国乳腺癌内分泌治疗多学科管理血脂异常管理共识专家组. 绝经后早期乳腺癌患者血脂异常管理的中国专家共识[J]. 中华肿瘤杂志, 2017, 39(1): 72-77.
	China breast cancer Endocrine Therapy Multidisciplinary Management Lipid Abnormality Management Consensus Expert Group. China expert consensus on the management of dyslipidemia in postmenopausal patients with early- stage breast cancer[J]. Chin J Oncol, 2017, 39(1): 72-77.
[66]	COOMBES R C, KILBURN L S, SNOWDON C F, et al. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial[J]. Lancet, 2007, 369(9561): 559-570. pmid: 17307102
[67]	BOCCARDO F, RUBAGOTTI A, PUNTONI M, et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian tamoxifen anastrozole trial[J]. J Clin Oncol, 2005, 23(22): 5138-5147. pmid: 16009955
[68]	ARIMIDEX T, BUZDAR A, HOWELL A, et al. Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial[J]. Lancet Oncol, 2006, 7(8): 633-643. pmid: 16887480
[69]	COATES A S, KESHAVIAH A, THÜRLIMANN B, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98[J]. J Clin Oncol, 2007, 25(5): 486-492. pmid: 17200148
[70]	GOSS P E, INGLE J N, PRITCHARD K I, et al. Exemestane versus anastrozole in postmenopausal women with early breast cancer: Ncic ctg ma.27: a randomized controlled phase Ⅲ trial[J]. J Clin Oncol, 2013, 31(11): 1398-1404. doi: 10.1200/JCO.2012.44.7805
[71]	HOWELL A, ROBERTSON J F, QUARESMA ALBANO J, et al. Fulvestrant, formerly ICI 182, 780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment[J]. J Clin Oncol, 2002, 20(16): 3396-3403. doi: 10.1200/JCO.2002.10.057
[72]	OSBORNE C K, PIPPEN J, JONES S E, et al. Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial[J]. J Clin Oncol, 2002, 20(16): 3386-3395. pmid: 12177098
[73]	WANG X, ZHU A J, WANG J Y, et al. Steroidal aromatase inhibitors have a more favorable effect on lipid profiles than nonsteroidal aromatase inhibitors in postmenopausal women with early breast cancer: a prospective cohort study[J]. Ther Adv Med Oncol, 2020, 12: 1758835920925991.
[74]	MARKOPOULOS C, POLYCHRONIS A, DAFNI U, et al. Lipid changes in breast cancer patients on exemestane treatment: final results of the TEAM Greek substudy[J]. Ann Oncol, 2009, 20(1): 49-55. doi: 10.1093/annonc/mdn545 pmid: 18678766
[75]	CAMERINI A, RONDINI M, GARRONE O, et al. Fulvestrant treatment is associated with cholesterol plasma level reduction in hormone-receptor-positive metastatic breast cancer patients[J]. Cancer Biol Ther, 2009, 8(15): 1450-1455. pmid: 19556864
[76]	GOEDEGEBUURE W J, VAN DER STEEN M, KERKHOF G F, et al. Longitudinal study on metabolic health in adults SGA during 5 years after GH with or without 2 years of GnRHa treatment[J]. J Clin Endocrinol Metab, 2020, 105(8): dgaa287.
[77]	YANNUCCI J, MANOLA J, GARNICK M B, et al. The effect of androgen deprivation therapy on fasting serum lipid and glucose parameters[J]. J Urol, 2006, 176(2): 520-525. doi: 10.1016/j.juro.2006.03.057 pmid: 16813881
[78]	诸骏仁, 高润霖, 赵水平, 等. 中国成人血脂异常防治指南(2016年修订版)[J]. 中国循环杂志, 2016, 31(10): 937-953.
	ZHU J R, GAO R L, ZHAO S P, et al. Guidelines for the prevention and treatment of dyslipidemia in Chinese adults (revised in 2016)[J]. Chin Circ J, 2016, 31(10): 937-953.
[79]	TAUNK N K, HAFFTY B G, KOSTIS J B, et al. Radiation-induced heart disease: pathologic abnormalities and putative mechanisms[J]. Front Oncol, 2015, 5: 39. doi: 10.3389/fonc.2015.00039 pmid: 25741474
[80]	SOUMAROVÁ R, RUŠINOVÁ L. Cardiotoxicity of breast cancer radiotherapy-overview of current results[J]. Rep Pract Oncol Radiother, 2020, 25(2): 182-186. doi: 10.1016/j.rpor.2019.12.008
[81]	CLARKE M, COLLINS R, DARBY S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials[J]. Lancet, 2005, 366(9503): 2087-2106. doi: 10.1016/S0140-6736(05)67887-7 pmid: 16360786
[82]	HENSON K E, MCGALE P, TAYLOR C, et al. Radiation-related mortality from heart disease and lung cancer more than 20 years after radiotherapy for breast cancer[J]. Br J Cancer, 2013, 108(1): 179-182. doi: 10.1038/bjc.2012.575
[83]	CHENG Y J, NIE X Y, JI C C, et al. Long-term cardiovascular risk after radiotherapy in women with breast cancer[J]. J Am Heart Assoc, 2017, 6(5): e005633. doi: 10.1161/JAHA.117.005633
[84]	LANCELLOTTI P, NKOMO V T, BADANO L P, et al. Expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults: a report from the European Association of Cardiovascular Imaging and the American Society of Echocardiography[J]. Eur Heart J Cardiovasc Imaging, 2013, 14(8): 721-740. doi: 10.1093/ehjci/jet123 pmid: 23847385
[85]	SAIKI H, PETERSEN I A, SCOTT C G, et al. Risk of heart failure with preserved ejection fraction in older women after contemporary radiotherapy for breast cancer[J]. Circulation, 2017, 135(15): 1388-1396. doi: 10.1161/CIRCULATIONAHA.116.025434 pmid: 28132957
[86]	DARBY S C, EWERTZ M, MCGALE P, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer[J]. N Engl J Med, 2013, 368(11): 987-998. doi: 10.1056/NEJMoa1209825
[87]	TAYLOR C, CORREA C, DUANE F K, et al. Estimating the risks of breast cancer radiotherapy: evidence from modern radiation doses to the lungs and heart and from previous randomized trials[J]. J Clin Oncol, 2017, 35(15): 1641-1649. doi: 10.1200/JCO.2016.72.0722 pmid: 28319436
[88]	NILSSON G, HOLMBERG L, GARMO H, et al. Distribution of coronary artery stenosis after radiation for breast cancer[J]. J Clin Oncol, 2012, 30(4): 380-386. doi: 10.1200/JCO.2011.34.5900 pmid: 22203772
[89]	LO Q, HEE L A, BATUMALAI V, et al. Strain imaging detects dose-dependent segmental cardiac dysfunction in the acute phase after breast irradiation[J]. Int J Radiat Oncol Biol Phys, 2017, 99(1): 182-190. doi: 10.1016/j.ijrobp.2017.05.030
[90]	VAN DEN BOGAARD V A, TA B D, et al. VAN DER SCHAAF A, Validation and modification of a prediction model for acute cardiac events in patients with breast cancer treated with radiotherapy based on three-dimensional dose distributions to cardiac substructures[J]. J Clin Oncol, 2017, 35(11): 1171-1178. doi: 10.1200/JCO.2016.69.8480 pmid: 28095159
[91]	ZAGAR T M, KAIDAR-PERSON O, TANG X L, et al. Utility of deep inspiration breath hold for left-sided breast radiation therapy in preventing early cardiac perfusion defects: a prospective study[J]. Int J Radiat Oncol Biol Phys, 2017, 97(5): 903-909. doi: 10.1016/j.ijrobp.2016.12.017
[92]	CHANG J S, CHEN J, WEINBERG V K, et al. Evaluation of heart dose for left-sided breast cancer patients over an 11-year period spanning the transition from 2-dimensional to 3-dimensional planning[J]. Clin Breast Cancer, 2016, 16(5): 396-401. doi: S1526-8209(16)30109-4 pmid: 27292181
[93]	REMOUCHAMPS V M, VICINI F A, SHARPE M B, et al. Significant reductions in heart and lung doses using deep inspiration breath hold with active breathing control and intensity-modulated radiation therapy for patients treated with locoregional breast irradiation[J]. Int J Radiat Oncol Biol Phys, 2003, 55(2): 392-406. doi: 10.1016/S0360-3016(02)04143-3
[94]	GOYAL U, SABODA K, ROE D, et al. Prone positioning with deep inspiration breath hold for left breast radiotherapy[J]. Clin Breast Cancer, 2021, 21(4): e295-e301. doi: 10.1016/j.clbc.2020.11.004 pmid: 33358601
[95]	TAYLOR C W, WANG Z, MACAULAY E, et al. Exposure of the heart in breast cancer radiation therapy: a systematic review of heart doses published during 2003 to 2013[J]. Int J Radiat Oncol Biol Phys, 2015, 93(4): 845-853. doi: 10.1016/j.ijrobp.2015.07.2292
[96]	MACDONALD S M, JIMENEZ R, PAETZOLD P, et al. Proton radiotherapy for chest wall and regional lymphatic radiation; dose comparisons and treatment delivery[J]. Radiat Oncol, 2013, 8: 71. doi: 10.1186/1748-717X-8-71 pmid: 23521809
[97]	ZAMORANO J L, LANCELLOTTI P, RODRIGUEZ MUÑOZ D, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for practice guidelines[J]. Eur J Heart Fail, 2017, 19(1): 9-42. doi: 10.1002/ejhf.654
[98]	NELLESSEN U, ZINGEL M, HECKER H, et al. Effects of radiation therapy on myocardial cell integrity and pump function: which role for cardiac biomarkers?[J]. Chemotherapy, 2010, 56(2): 147-152. doi: 10.1159/000313528 pmid: 20407242
[99]	SKYTTÄ T, TUOHINEN S, BOMAN E, et al. Troponin T-release associates with cardiac radiation doses during adjuvant left-sided breast cancer radiotherapy[J]. Radiat Oncol, 2015, 10: 141. doi: 10.1186/s13014-015-0436-2 pmid: 26159409
[100]	DEVEREAUX P J, GOLDMAN L, COOK D J, et al. Perioperative cardiac events in patients undergoing noncardiac surgery: a review of the magnitude of the problem, the pathophysiology of the events and methods to estimate and communicate risk[J]. CMAJ, 2005, 173(6): 627-634. pmid: 16157727
[101]	FLEISHER L A, FLEISCHMANN K E, AUERBACH A D, et al. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Developed in collaboration with the American College of Surgeons, American Society of Anesthesiologists, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Anesthesiologists, and Society of Vascular Medicine Endorsed by the Society of Hospital Medicine[J]. J Nucl Cardiol, 2015, 22: 162-215. doi: 10.1007/s12350-014-0025-z
[102]	JENSEN B V. Cardiotoxic consequences of anthracycline-containing therapy in patients with breast cancer[J]. Semin Oncol, 2006, 33(<W>3 Suppl 8): S15-S21. doi: 10.1053/j.seminoncol.2006.08.003
[103]	OKAMOTO T, OGATA J, MINAMI K. Sino-atrial block during anesthesia in a patient with breast cancer being treated with the anticancer drug epirubicin[J]. Anesth Analg, 2003, 97(1): 19-20, tableofcontents. pmid: 12818936
[104]	HUETTEMANN E, JUNKER T, CHATZINIKOLAOU K P, et al. The influence of anthracycline therapy on cardiac function during anesthesia[J]. Anesth Analg, 2004, 98(4): 941-947. doi: 10.1213/01.ANE.0000108135.52036.48 pmid: 15041577
[105]	KOJIMA A, KITAGAWA H, OMATSU-KANBE M, et al. Sevoflurane protects ventricular myocytes against oxidative stress-induced cellular Ca2+ overload and hypercontracture[J]. Anesthesiology, 2013, 119(3): 606-620. doi: 10.1097/ALN.0b013e318292ee52 pmid: 23571639
[106]	樊理华, 韩新, 陈琴. 七氟烷对术前化疗患者心肌细胞的影响[J]. 浙江医学, 2013, 35(15): 1422-1423.
	FAN L H, HAN X, CHEN Q. Sevoflurane does not aggravate myocardial injury induced by preoperative chemotherapy[J]. Zhejiang Med J, 2013, 35(15): 1422-1423.
[107]	赵光瑜, 王永顺, 代冬梅, 陈筠. 乳腺癌患者术前化疗及不同麻醉方法对血液流变学的影响[J]. 临床麻醉学杂志, 2002, 18(3): 124-126.
	ZHAO G Y, WANG Y S, DAI D M, et al. Effects of anesthesia on hemorheology in breast cancer patient underwent chemotherapy[J]. J Clin Anesth, 2002, 18(3): 124-126. doi: 10.1016/j.jclinane.2005.08.013
[108]	KRISTENSEN S D, KNUUTI J, SARASTE A, et al. 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The joint task force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA)[J]. Eur Heart J, 2014, 35(35): 2383-2431. doi: 10.1093/eurheartj/ehu282
[109]	LARSEN C M, MULVAGH S L. Cardio-oncology: What you need to know now for clinical practice and echocardiography[J]. Echo Res Pract, 2017, 4(1): R33-R41. doi: 10.1530/ERP-17-0013
[110]	CURIGLIANO G, CARDINALE D, SUTER T, et al. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO clinical practice guidelines[J]. Ann Oncol, 2012, 23(Suppl 7): vii155-vii166. doi: 10.1093/annonc/mds293
[111]	VIRANI S A, DENT S, BREZDEN-MASLEY C, et al. Canadian cardiovascular society guidelines for evaluation and management of cardiovascular complications of cancer therapy[J]. Can J Cardiol, 2016, 32(7): 831-841. doi: 10.1016/j.cjca.2016.02.078 pmid: 27343741
[112]	CURIGLIANO G, LENIHAN D, FRADLEY M, et al. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations[J]. Ann Oncol, 2020, 31(2): 171-190. doi: S0923-7534(19)36080-6 pmid: 31959335
[113]	SUN J P, POPOVIĆ Z B, GREENBERG N L, et al. Noninvasive quantification of regional myocardial function using Doppler-derived velocity, displacement, strain rate, and strain in healthy volunteers: effects of aging[J]. J Am Soc Echocardiogr, 2004, 17(2): 132-138. doi: 10.1016/j.echo.2003.10.001
[114]	JORDAN J H, SUKPRAPHRUTE B, MELÉNDEZ G C, et al. Early myocardial strain changes during potentially cardiotoxic chemotherapy may occur as a result of reductions in left ventricular end-diastolic volume: The need to interpret left ventricular strain with volumes[J]. Circulation, 2017, 135(25): 2575-2577. doi: 10.1161/CIRCULATIONAHA.117.027930 pmid: 28630272
[115]	MELÉNDEZ G C, SUKPRAPHRUTE B, D'AGOSTINO R B Jr, et al. Frequency of left ventricular end-diastolic volume-mediated declines in ejection fraction in patients receiving potentially cardiotoxic cancer treatment[J]. Am J Cardiol, 2017, 119(10): 1637-1642. doi: S0002-9149(17)30194-7 pmid: 28341361
[116]	FALLAH-RAD N, WALKER J R, WASSEF A, et al. The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor II-positive breast cancer treated with adjuvant trastuzumab therapy[J]. J Am Coll Cardiol, 2011, 57(22): 2263-2270. doi: 10.1016/j.jacc.2010.11.063
[117]	NEGISHI K, NEGISHI T, HALUSKA B A, et al. Use of speckle strain to assess left ventricular responses to cardiotoxic chemotherapy and cardioprotection[J]. Eur Heart J Cardiovasc Imaging, 2014, 15(3): 324-331. doi: 10.1093/ehjci/jet159 pmid: 24057661
[118]	SAWAYA H, SEBAG I A, PLANA J C, et al. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab[J]. Circ Cardiovasc Imaging, 2012, 5(5): 596-603. doi: 10.1161/CIRCIMAGING.112.973321 pmid: 22744937
[119]	SANTORO C, ARPINO G, ESPOSITO R, et al. 2D and 3D strain for detection of subclinical anthracycline cardiotoxicity in breast cancer patients: a balance with feasibility[J]. Eur Heart J Cardiovasc Imaging, 2017, 18(8): 930-936. doi: 10.1093/ehjci/jex033 pmid: 28379383
[120]	CHANG W T, SHIH J Y, FENG Y H, et al. The early predictive value of right ventricular strain in epirubicin-induced cardiotoxicity in patients with breast cancer[J]. Acta Cardiol Sin, 2016, 32(5): 550-559.
[121]	LANG R M, BADANO L P, MOR-AVI V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging[J]. Eur Heart J Cardiovasc Imaging, 2015, 16(3): 233-270. doi: 10.1093/ehjci/jev014 pmid: 25712077
[122]	BERGAMINI C, DOLCI G, ROSSI A, et al. Left atrial volume in patients with HER2-positive breast cancer: one step further to predict trastuzumab-related cardiotoxicity[J]. Clin Cardiol, 2018, 41(3): 349-353. doi: 10.1002/clc.22872 pmid: 29569424
[123]	TOTZECK M, SCHULER M, STUSCHKE M, et al. Cardio-oncology - strategies for management of cancer-therapy related cardiovascular disease[J]. Int J Cardiol, 2019, 280: 163-175. doi: S0167-5273(18)35860-1 pmid: 30661849
[124]	FRADLEY M G, MOSLEHI J. QT prolongation and oncology drug development[J]. Card Electrophysiol Clin, 2015, 7(2): 341-355. doi: 10.1016/j.ccep.2015.03.013 pmid: 26002398
[125]	HORTOBAGYI G N, STEMMER S M, BURRIS H A, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer[J]. N Engl J Med, 2016, 375(18): 1738-1748. doi: 10.1056/NEJMoa1609709
[126]	THYGESEN K, ALPERT J S, JAFFE A S, et al. Fourth universal definition of myocardial infarction (2018)[J]. Circulation, 2018, 138(20): e618-e651.
[127]	TWERENBOLD R, BOEDDINGHAUS J, NESTELBERGER T, et al. Clinical use of high-sensitivity cardiac troponin in patients with suspected myocardial infarction[J]. J Am Coll Cardiol, 2017, 70(8): 996-1012. doi: S0735-1097(17)38777-6 pmid: 28818210
[128]	MAIR J, LINDAHL B, MÜLLER C, et al. What to do when you question cardiac troponin values[J]. Eur Heart J Acute Cardiovasc Care, 2018, 7(6): 577-586. doi: 10.1177/2048872617708973 pmid: 28485179
[129]	BERRY G J, JORDEN M. Pathology of radiation and anthracycline cardiotoxicity[J]. Pediatr Blood Cancer, 2005, 44(7): 630-637. pmid: 15825155
[130]	GOLDHAR H A, YAN A T, KO D T, et al. The temporal risk of heart failure associated with adjuvant trastuzumab in breast cancer patients: a population study[J]. J Natl Cancer Inst, 2016, 108(1): djv301. doi: 10.1093/jnci/djv301
[131]	CHOW E J, BAKER K S, LEE S J, et al. Influence of conventional cardiovascular risk factors and lifestyle characteristics on cardiovascular disease after hematopoietic cell transplantation[J]. J Clin Oncol, 2014, 32(3): 191-198. doi: 10.1200/JCO.2013.52.6582 pmid: 24297944
[132]	ADVANI P P, BALLMAN K V, DOCKTER T J, et al. Long-term cardiac safety analysis of NCCTG N9831 (alliance) adjuvant trastuzumab trial[J]. J Clin Oncol, 2016, 34(6): 581-587. doi: 10.1200/JCO.2015.61.8413 pmid: 26392097
[133]	PINDER M C, DUAN Z G, GOODWIN J S, et al. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer[J]. J Clin Oncol, 2007, 25(25): 3808-3815. pmid: 17664460
[134]	CARDINALE D, COLOMBO A, BACCHIANI G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy[J]. Circulation, 2015, 131(22): 1981-1988. doi: 10.1161/CIRCULATIONAHA.114.013777 pmid: 25948538
[135]	CARDINALE D, COLOMBO A, LAMANTIA G, et al. Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy[J]. J Am Coll Cardiol, 2010, 55(3): 213-220. doi: 10.1016/j.jacc.2009.03.095 pmid: 20117401
[136]	ARMENIAN S H, LACCHETTI C, BARAC A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline[J]. J Clin Oncol, 2017, 35(8): 893-911. doi: 10.1200/JCO.2016.70.5400 pmid: 27918725
[137]	KIKUCHI R, SHAH N P, DENT S F. Strategies to prevent cardiovascular toxicity in breast cancer: is it ready for primetime?[J]. J Clin Med, 2020, 9(4): 896. doi: 10.3390/jcm9040896
[138]	AVILA M S, AYUB-FERREIRA S M, DE BARROS WANDERLEY M R Jr, et al. Carvedilol for prevention of chemotherapy-related cardiotoxicity: the CECCY trial[J]. J Am Coll Cardiol, 2018, 71(20): 2281-2290. doi: S0735-1097(18)33480-6 pmid: 29540327
[139]	BOEKHOUT A H, GIETEMA J A, MILOJKOVIC KERKLAAN B, et al. Angiotensin II-receptor inhibition with candesartan to prevent trastuzumab-related cardiotoxic effects in patients with early breast cancer: a randomized clinical trial[J]. JAMA Oncol, 2016, 2(8): 1030-1037. doi: 10.1001/jamaoncol.2016.1726 pmid: 27348762
[140]	GULATI G, HECK S L, REE A H, et al. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol[J]. Eur Heart J, 2016, 37(21): 1671-1680. doi: 10.1093/eurheartj/ehw022 pmid: 26903532
[141]	PITUSKIN E, MACKEY J R, KOSHMAN S, et al. Multidisciplinary approach to novel therapies in cardio-oncology research (MANTICORE 101-breast): a randomized trial for the prevention of trastuzumab-associated cardiotoxicity[J]. J Clin Oncol, 2017, 35(8): 870-877. doi: 10.1200/JCO.2016.68.7830 pmid: 27893331
[142]	GUGLIN M, KRISCHER J, TAMURA R, et al. Randomized trial of lisinopril versus carvedilol to prevent trastuzumab cardiotoxicity in patients with breast cancer[J]. J Am Coll Cardiol, 2019, 73(22): 2859-2868.
[143]	GEUNA E, LOMBARDI P, MARTINELLO R, et al. Treatment with beta-blockers and ACE-inhibitors in breast cancer patients receiving adjuvant trastuzumab-based therapy and developing mild cardiac toxicity: a prospective study[J]. Cancers (Basel), 2020, 12(2): E327.
[144]	中国抗癌协会乳腺癌专业委员会. 中国抗癌协会乳腺癌诊治指南与规范(2021年版)[J]. 中国癌症杂志, 2021, 31(10): 954-1040.
	The Society of Breast Cancer China Anti-Cancer Association. Guidelines for breast cancer diagnosis and treatment by China Anti-Cancer Association (2021 edition)[J]. China Oncol, 2021, 31(10): 954-1040.

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