曲妥珠单抗辅助治疗26例HER2阳性乳腺癌患者长期心脏毒性观察

付强; 夏曙; 黎春蕾; 于世英

doi:10.3969/j.issn.1000-8179.2012.23.021

曲妥珠单抗辅助治疗26例HER2阳性乳腺癌患者长期心脏毒性观察

doi: 10.3969/j.issn.1000-8179.2012.23.021

付强^①,
夏曙^①,
黎春蕾^②,
于世英^①, ,

①.
华中科技大学同济医学院附属同济医院肿瘤中心（武汉市430030）
②.
华中科技大学同济医学院附属同济医院超声影像科

详细信息

通讯作者:
于世英 syyu@tjh.tmu.edu.cn

计量
- 文章访问数: 54
- HTML全文浏览量: 2
- PDF下载量: 0
- 被引次数: 0
出版历程
- 收稿日期: 2011-09-19
- 修回日期: 2012-01-29

Analysis of Long-term Cardiotoxicity of Adjuvant Trastuzumab Therapy in HER2-positive Breast Cancer Patients

Qiang FU^①,
Shu XIA^①,
Chun-lei LI^②,
Shiying YU^{①
, ,}

①.
Department of Cancer Center, Tongji Hospital of Tongji Medical College, Hua Zhong University of Science and Technology, Wuhan430030, China
②.
Department of Medical Ultrasound, Tongji Hospital of Tongji Medical College, Hua Zhong University of Science and Technology, Wuhan430030, China

More Information

Corresponding author: Shiying YU; E-mail: syyu@tjh.tmu.edu.cn

摘要

摘要: 目的研究HER2阳性乳腺癌患者应用曲妥珠单抗治疗的心脏远期毒性反应。方法收集31例可手术且HER2阳性表达乳腺癌患者, HER2阳性表达定义为免疫组织化学方法(3+)或荧光原位杂交方法确认HER2基因扩增, 其中26例接受每3周1次的曲妥珠单抗治疗, 首次以负荷剂量8 mg/kg给药, 后每3周6 mg/kg维持治疗; 采用心脏二维超声定期监测左心射血分数(LVEF), 评估心脏毒性反应。结果曲妥珠单抗首次用药后随访期79~104个月, 中位随访90个月, 26例患者接受曲妥珠单抗治疗6个月和12个月为2例, 1年治疗为14例, 2年为10例。2例出现症状性左心射血分数下降, 降幅超过10%, 且1例伴有高血压患者出现心衰症状, 经对症处理1年后LVEF值仍为41%。辅助化疗使用过蒽环类对比未使用过蒽环类药物LVEF均值治疗前为(64.38±5.25)%, 使用1年后为(61.58±4.97)%, 使用5年后为(60.04±5.73)%(P > 0.05)。结论曲妥珠单抗总体安全性良好, 心脏毒性虽为可逆性, 但对具有高血压及心脏疾患的老年乳腺癌患者, 仍须注意评估与监测。
- 乳腺癌 /
- 曲妥珠单抗 /
- 心脏毒性
Abstract: Objective To investigate long-term cardiotoxicity in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with trastuzumab. Methods We gathered operable, HER2-positive breast cancer patients in Tongji Hospital from January 2002 to January 2005. HER2 positive was defined protein expression (3+) measured by immunohistochemistry or Her2 gene amplification by fluorescence in situ hybridization. A total of 26 cases received 6 mg/kg of trastuzumab every 3 weeks after a loading dose of 8 mg/kg. The left ventricular ejection fraction (LVEF) was measured for regular monitoring and assessment of cardiotoxicity. Results All cases were followed up 79 months to 104 months after the first trastuzumab administration. The median follow-up time was 90 months. Two patients were treated with trastuzumab for less than 1 year, 14 cases were treated for 1 year, and 10 cases were treated for 2 years. A symptomatic decline in LVEF occurred in 2 cases, representing a decrease of more than 10%. In addition, 1 case with hypertension manifested symptoms of heart failure and an LVEF value at 41% after 1 year of cardiac treatment. Comparison between adjuvant chemotherapy with anthracycline and chemotherapy without anthracycline obtained the baseline mean LVEF value of 64.38%± 5.25%. The value was 61.58% ± 4.97% after 1 year of trastuzumab treatment and 60.04% ± 5.73% after 5 years of trastuzumab treatment (P > 0.05). Conclusion Trastuzumab administration was generally safe, with reversible cardiac toxicity. However, this treatment should be evaluated and monitored in elderly breast cancer patients with hypertension and heart disease.
- Breast cancer /
- Trastuzumab /
- Cardiotoxicity

HTML全文

表 1 26例HER2阳性乳腺癌患者临床特征

Table 1. The clinical characteristics of 26 patients

表 2 曲妥珠单抗治疗前、治疗后1年及5年LVEF值与蒽环类药物化疗相关分析

Table 2. Correlation analysis of LVEF value and Anthracycline when trastuzumab was given before treatment, treatment after 1 year and 5 years

参考文献(14)

[1]	Doyle DM, Miller KD. Development of new targeted therapies for breast cancer[J]. Breast Cancer, 2008, 15(1): 49-56. doi: 10.1007/s12282-007-0003-2
[2]	张勤, 刘红, 赵晶. 人表皮生长因子受体-2在雌孕激素双阴性乳腺癌中的表达及作用[J]. 中国肿瘤临床, 2011, 38(3): 138-142. doi: 10.3969/j.issn.1000-8179.2011.03.005
[3]	Slamon D, Eiermann W, Robert N, et al. Adjuvant?trastuzumab in? HER2-positive breast cancer[J]. N Engl J Med, 2011, 365(14): 1273-1283. doi: 10.1056/NEJMoa0910383
[4]	Moja L, Tagliabue L, Balduzzi S, et al. Trastuzumab containing regimens for early breast cancer[J]. Cochrane Database Syst Rev, 2012, 4: CD006243.
[5]	李晓玲, 王育琴. 曲妥珠单抗心脏毒性及防治策略[J]. 药物不良反应杂志, 2009, 11(4): 257-259.
[6]	Ewer MS, Vooletich MT, Durand JB, et al. Reversibility of trastuzumab related cardiotoxicity: new insights based on clinical course and response tomedical treatment[J]. J Clin Oncol, 2005, 23(31): 7820-7826. doi: 10.1200/JCO.2005.13.300
[7]	Verma S, Ewer MS. Is cardiotoxicity being adequately assessed in current trials of cytotoxic and targeted agents in breast cancer[J]? Ann Oncol, 2011, 22(5): 1011-1018. doi: 10.1093/annonc/mdq607
[8]	Yood MU, Wells KE, Alford SH, et al. Cardiovascular outcomes in women with advanced breast cancer exposed to chemotherapy[J]. Pharmacoepidemiol Drug Saf, 2012, 21(8): 818-827. doi: 10.1002/pds.3239
[9]	Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2- positive breast cancer[J]. N engl J Med, 2005, 353(16): 1673-1684. doi: 10.1056/NEJMoa052122
[10]	Ning Y, Shen Q, Herrick K, et al. Cause of death in cancer survivors. AACR Annual Meeting, 2012, Abstract: LB-339.
[11]	Perez EA, Suman VJ, Davidson NE, 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
[12]	付强, 于世英. HER2和ER/PR双阳性表达的Ⅰ~Ⅲ期乳腺癌患者生存分析[J]. 中国肿瘤临床, 2009, 36(18): 1051-1053. doi: 10.3969/j.issn.1000-8179.2009.18.010
[13]	Gonzalez-Angulo AM, Hortobagyi GN. Is there an ideal way to combine trastuzumab with chemotherapy[J]. J Clin Oncol, 2011, 29(34): 4474-4476. doi: 10.1200/JCO.2011.38.3836
[14]	Morris PG, Chen C, Steingart R, et al. Troponin I and C-reactive protein are commonly detected in patients with breast cancer treated with dose-dense chemotherapy incorporating trastuzumab and lapatinib[J]. Clin Cancer Res, 2011, 17(10): 3490-3499. doi: 10.1158/1078-0432.CCR-10-1359