蒽环类化疗药物致乳腺癌患者发生急性心脏毒性的危险因素研究

doi:10.3760/cma.j.issn.1007-1245.2024.01.022

摘要/Abstract

摘要：

目的　探讨蒽环类化疗药物致乳腺癌患者发生急性心脏毒性的危险因素。方法　对2021年6月至2023年6月于安阳市肿瘤医院接受蒽环类药物化疗的280例乳腺癌患者的临床资料进行回顾性分析，所有患者均为女性，年龄38～67（52.13±8.43）岁，体质量指数19～25（22.49±2.12）kg/m²，采集所有患者的一般资料并按照急性心脏毒性的相关判定标准将所有患者分为发生组（125例）和未发生组（155例）。将两组患者基线资料进行对比，将基线资料中差异有统计学意义的因素纳入多因素logistic回归分析模型，对蒽环类化疗药物致乳腺癌患者发生急性心脏毒性的危险因素进行筛选，采用t检验、χ²检验进行统计学分析。结果　急性心脏毒性的发生率为44.64%（125/280），其中同时出现两种以上心电图异常的患者为4.00%（5/125）。患者急性心脏毒性均发生在化疗完成后半年内，且患者的临床表现均为心电图异常，较为常见的为窦性心动过速［26.40%（33/125）］、QTC间期改变［22.40%（28/125）］、T波改变［16.80%（21/125）］等；单因素分析结果显示，发生组年龄≥55岁、已绝经、有糖尿病病史、有高血压病史、有高血脂病史、联合曲妥珠单抗、联合右雷佐生的患者占比相较于未发生组高［32.00%（40/125）比21.29%（33/155）、60.00%（75/125）比18.71%（29/155）、31.20%（39/125）比6.45%（10/155）、29.60%（37/125）比12.90%（20/155）、16.00%（20/125）比7.74%（12/155）、28.00%（35/125）比12.90%（20/155）、72.80%（91/125）比41.94%（65/155）］，发生组患者肌酸激酶同工酶、α-羟丁酸脱氢酶（α-HBDH）均比未发生组高［（16.02±6.00）U/L比（12.54±5.01）U/L、（139.78±31.75）U/L比（132.78±20.45）U/L］，差异均有统计学意义（χ²=4.12、50.53、29.36、11.90、4.66、9.99、26.72，t=5.289、2.23，均P<0.05）；多因素logistic回归分析结果显示，年龄、绝经、糖尿病病史、联合曲妥珠单抗、肌酸激酶同工酶、α-HBDH是蒽环类化疗药物致乳腺癌患者发生急性心脏毒性的危险因素（OR=1.015、17.133、1.744、4.096、4.175、2.085，均P<0.05），而联合右雷佐生则是蒽环类化疗药物致乳腺癌患者发生急性心脏毒性的保护因素（OR=0.613，P<0.05）。结论　年龄、绝经、糖尿病病史、联合曲妥珠单抗、肌酸激酶同工酶、α-HBDH是蒽环类化疗药物致乳腺癌患者发生急性心脏毒性的危险因素，而联合右雷佐生则是蒽环类化疗药物致乳腺癌患者发生急性心脏毒性的保护因素，临床可据此采取相关措施，以降低急性心脏毒性的发生率。

关键词:

乳腺癌, 蒽环素, 化疗药物, 急性心脏毒性, 危险因素

Abstract:

Objective　To investigate the risk factors of acute cardiotoxicity induced by anthracyclines in patients with breast cancer. Methods　The clinical data of 280 female patients with breast cancer who received anthracycline chemotherapy in Anyang Tumor Hospital from June 2021 to June 2023 were retrospectively analyzed. They were 38 to 67 (52.13±8.43) years old. Their body mass index (BMI) was 19 to 25 (22.49±2.12) kg/m². The general data of all the patients were collected. They were divided into an occurrence group (125 cases) and a non-occurrence group (155 cases) according to the criteria of acute cardiotoxicity. The baseline data of the two groups were compared; the factors with statistical significance in the baseline data were included into the multivariate logistic regression analysis model to screen the risk factors for acute cardiotoxicity in the patients. The statistical analysis was performed by t and χ² tests. Results　The incidence of acute cardiotoxicity was 44.64% (125/280); among them, 5 cases (4.00%, 5/125) had two or more electrocardiograph abnormalities. Acute cardiotoxicity occurred in all the patients within six months after the completion of chemotherapy, and the clinical manifestations of all the patients were abnormal electrocardiogram; the more common ones were sinus tachycardia [26.40% (33/125)], QTC interval change [22.40% (28/125)], T wave change [16.80% (21/125)], etc. The results of univariate analysis showed that the proportions of the patients ≥ 55 years old, with menopause, with history of diabetes, with history of hypertension, with history of hyperlipidemia, and who took the combination of trastuzumab and the combination of dextrazone in the occurrence group was higher than those in the non-occurrence group [32.00% (40/125) vs. 21.29% (33/155), 60.00% (75/125) vs. 18.71% (29/155), 31.20% (39/125) vs. 6.45% (10/155), 29.60% (37/125) vs. 12.90% (20/155), 16.00% (20/125) vs. 7.74% (12/155), 28.00% (35/125) vs. 12.90% (20/155), and 72.80% (91/125) vs. 41.94% (65/155)]; the levels of creatine kinase isoenzyme and α-hydroxybutyrate dehydrogenase in the occurrence group were higher than those in the non-occurrence group [(16.02±6.00) U/L vs. (12.54±5.01) U/L and (139.78±31.75) U/L vs. (132.78±20.45) U/L]; there were statistical differences (χ²=4.12, 50.53, 29.36, 11.90, 4.66, 9.99, and 26.72; t=5.29 and 2.23; all P<0.05). The results of multivariate logistic regression analysis showed that age, menopause, diabetes history, combined trastuzumab, creatine kinase isoenzyme, and α-hydroxybutyrate dehydrogenase were the risk factors for acute cardiotoxicity in the patients (OR=1.015, 17.133, 1.744, 4.096, 4.175, and 2.085; all P<0.05); combined dexrazoxane was a protective factor against acute cardiotoxicity in the patients (OR=0.613, P<0.05). Conclusions　Age, menopause, diabetes history, combined trastuzumab, creatine kinase isoenzyme, and α-hydroxybutyrate dehydrogenase are risk factors for acute cardiotoxicity induced by anthracycline chemotherapy in patients with breast cancer, while combined dexrazoxane is a protective factor. Therefore, relevant clinical measures should be taken accordingly to reduce the incidence of acute cardiotoxicity.

Key words:

Breast cancer, Anthracyclines, Chemotherapy drugs, Acute cardiotoxicity, Risk factors

侯西栋周丽华温艳艳.

蒽环类化疗药物致乳腺癌患者发生急性心脏毒性的危险因素研究 [J]. 国际医药卫生导报, 2024, 30(1): 103-108.

Hou Xidong, Zhou Lihua, Wen Yanyan.

Risk factors of acute cardiotoxicity induced by anthracyclines in patients with breast cancer [J]. International Medicine and Health Guidance News, 2024, 30(1): 103-108.

参考文献

[1] 秦雪. 秦雪. TEC方案与EC-T序贯化疗对乳腺癌患者的疗效及对白细胞水平的影响[J]. 实用癌症杂志,2018,33(1):127-129,133. DOI:10.3969/j.issn.1001-5930.2018.01.039.
[2] 许小芳,柴姣,朱卫伟. 蒽环类药物化疗对乳腺癌术后患者血清心肌、氧化应激标志物及心脏彩超指标的影响及相关性[J]. 癌症进展,2021,19(2):167-170. DOI:10.11877/j.issn.1672-1535.2021.19.02.15.
[3] 李瑞春,李隆. 心脉隆注射液对乳腺癌化疗病人蒽环类药物治疗后内皮功能及氧化应激指标的影响[J]. 中西医结合心脑血管病杂志,2020,18(7):1130-1133. DOI:10.12102/j.issn.1672-1349.2020.07.025.
[4] 赵体贺,李湘奇. 蒽环类药物致乳腺癌患者心脏毒性的具体表现与防治策略[J]. 医学综述,2021,27(22):4452-4457. DOI:10.3969/j.issn.1006-2084.2021.22.015.
[5] 刘秀兰,裘琳. 不同疗程地塞米松联合阿瑞匹坦、托烷司琼预防蒽环类药物引起乳腺癌患者恶心及呕吐的临床研究[J]. 中国医院药学杂志,2020,40(5):549-551,569. DOI:10.13286/j.1001-5213.2020.05.15.
[6] 张萌萌,洛菲. 蒽环类药物治疗乳腺癌的心血管风险及对策[J]. 肿瘤研究与临床,2018,30(3):173-175,179. DOI:10.3760/cma.j.issn.1006-9801.2018.03.007.
[7] 呼改凤,付海霞,马继芳,等. 蒽环类药物对早期乳腺癌术后患者心脏毒性影响的临床研究[J]. 中华心血管病杂志,2018,46(12):987-992. DOI:10.3760/cma.j.issn.0253- 3758.2018.12.011.
[8] 宋秀莲,林婷,陈环梅. 利用二维斑点追踪成像技术评价化疗药物对乳腺癌患者左心功能损害的价值研究[J]. 国际医药卫生导报,2020,26(21):3217-3220.DOI:10.3760/cma.j.issn.1007-1245.2020.21.008.
[9] 杨娟,姜武忠. 曲美他嗪联合小剂量卡维地洛对乳腺癌患者蒽环类药物化疗后心脏毒性防治效果分析[J]. 临床和实验医学杂志,2018,17(1):57-60. DOI:10.3969/j.issn. 1671-4695.2018.01.018.
[10] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3):209-249. DOI: 10.3322/caac.21660.
[11] 曹司琪,陈勇,杨菲,等. 左心室心肌做功在乳腺癌患者蒽环类化疗药物心脏毒性评价中的应用价值[J]. 中华老年多器官疾病杂志,2021,20(5):337-342. DOI:10.11915/j.issn.1671-5403.2021.05.070.
[12] Hong YJ, Park HS, Park JK,et al. Early detection and serial monitoring of anthracycline-induced cardiotoxicity using T1-mapping cardiac magnetic resonance imaging: an animal study[J]. Sci Rep,2017,7(1):2663.DOI: 10.1038/s41598-017-02627-x.
[13] 董静,江佩,任俊怡,等. 实时三维斑点追踪成像对乳腺癌化疗患者心脏毒性的早期预测价值分析[J]. 中国临床医学影像杂志,2021,32(3):164-169. DOI:10.12117/jccmi. 2021.03.003.
[14] 贺飞,薄明明,梁锌,等. 蒽环类药物致乳腺癌患者急性心脏毒性的发生及影响因素的回顾性研究[J]. 中国药学杂志,2017,52(12):1089-1092. DOI:10.11669/cpj.2017.12.019.
[15] Dong Q, Ou W, Wang M, et al. Study on influencing factors of anthracycline-induced subclinical cardiotoxicity in DLBCL patients administered (R)-CHOP[J]. BMC Cancer,2022,22(1):988.DOI: 10.1186/s12885-022-10085-6.
[16] Cheraghi Z, Ayubi E, Doosti-Irani A. Obesity as a risk factor for anthracyclines and trastuzumab cardiotoxicity in breast cancer: methodologic issues to avoid misinterpretation in the meta-analysis[J]. J Clin Oncol,2017 ,35(8):923.DOI: 10.1200/JCO.2016.71.0715.
[17] 周彦君,李秋月,赵芳,等. HER2+乳腺癌患者蒽环类药物相关急性心脏毒性危险因素分析及预测模型构建[J]. 中国药学杂志,2023,58(6):527-532. DOI:10.11669/cpj. 2023.06.009.
[18] 董新江,尚茹茹,刘晓红. 蒽环类药物致乳腺癌患者校正QT间期延长的发生率及危险因素分析[J]. 中华全科医师杂志,2020,19(6):507-511. DOI:10.3760/cma.j.cn114798- 20191103-00803.
[19] 杨孟达,张鹏程,张迅,等. 右丙亚胺对表柔比星方案化疗乳腺癌患者表柔比星心脏毒性的预防作用观察[J]. 山东医药,2022,62(15):38-43. DOI:10.3969/j.issn.1002- 266X.2022.15.008.
[20] 齐宇新,刘姣,何颖娜,等. 乳腺癌术后蒽环类化疗药物致心脏损害的早期监测分析[J]. 中国药房,2017,28(17):2356-2359. DOI:10.6039/j.issn.1001-0408.2017.17.14.
[21] 侯欢,林晨,张敏,等. 新型抗肿瘤药物所致心脏毒性及分子机制研究进展[J]. 中国药学杂志,2022,57(1):8-14. DOI:10.11669/cpj.2022.01.002.
[22] 黄邹琴,柳子川,李涛,等. 蒽环类药物化疗对乳腺癌患者心肌损伤相关因素的影响[J]. 广东药学院学报,2016,32(3):383-386. DOI:10.16809/j.cnki.1006-8783.2016011203.
[23] Calvillo-Argüelles O, Abdel-Qadir H, Michalowska M,et al. Cardioprotective effect of statins in patients with HER2-positive breast cancer receiving trastuzumab therapy[J]. Can J Cardiol,2019,35(2):153-159. DOI: 10.1016/j.cjca.2018.11.028.
[24] 赵得堡,屈中玉,孙星,等. 蒽环类药物序贯曲妥珠单抗治疗导致乳腺癌患者心脏毒性的相关危险因素研究[J]. 广州医药,2023,54(3):105-108. DOI:10.3969/j.issn.1000-8535. 2023.03.020.
[25] 朱小丽,吕琛,杜雪亭,等. 蒽环类药物序贯曲妥珠单抗治疗导致乳腺癌患者心脏毒性的相关危险因素研究[J]. 中国医院用药评价与分析,2022,22(3):338-341. DOI:10.14009/j.issn.1672-2124.2022.03.019.
[26] 李婷,裴艺芳,张田,等. 注射用右雷佐生降低葸环类药物所致肿瘤患者心脏毒性的发生率和严重程度的快速卫生技术评估[J]. 中国药学杂志,2021,56(21):1764-1769. DOI:10.11669/cpj.2021.21.010.
[27] 任建林,武帅,贾红燕. 右丙亚胺联合稳心颗粒降低蒽环类药物致乳腺癌病人心脏毒性的临床疗效[J]. 中西医结合心脑血管病杂志,2020,18(16):2747-2749. DOI:10.12102/j.issn.1672-1349.2020.16.051.
[28] 谭雪莹,张晶,任卫东,等. 斑点追踪技术监测低剂量蒽环类药物对乳腺癌新辅助化疗患者的心脏毒性[J/CD]. 中华医学超声杂志(电子版),2021,18(2):143-149. DOI:10.3877/cma.j.issn.1672-6448.2021.02.004.
[29] 万梦婷,赵志玉,梅丹娥,等. 左室压力-应变环定量评估蒽环类药物化疗对乳腺癌患者左室功能的影响[J]. 临床超声医学杂志,2021,23(4):256-260. DOI:10.3969/j.issn. 1008-6978.2021.04.005.
[30] 王松,蒋刚. 蒽环类和曲妥珠单抗致乳腺癌患者心脏毒性的药物防治研究进展[J]. 肿瘤预防与治疗,2021,34(2):173-177. DOI:10.3969/j.issn.1674-0904.2021.02.014.