可溶性尿激酶型纤溶酶原激活物受体与阿霉素治疗的乳腺癌患者的心脏毒性：一项前瞻性探索性研究。
Soluble urokinase plasminogen activator receptor and cardiotoxicity in doxorubicin-treated breast cancer patients: a prospective exploratory study.
作者信息
Chu Jian, Tung Lillian, Atallah Issam, Wei Changli, Cobleigh Melody, Rao Ruta, Feinstein Steven B, Usha Lydia, Banach Kathrin, Reiser Jochen, Okwuosa Tochukwu M
机构信息
Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
Department of Internal Medicine, Division of Cardiology, Saint Louis University Hospital, St. Louis, MO, USA.
出版信息
Cardiooncology. 2024 Jan 15;10(1):3. doi: 10.1186/s40959-023-00191-0.
BACKGROUND
Soluble urokinase plasminogen activator receptor is an inflammatory biomarker that may prognosticate cardiovascular outcomes. We sought to determine the associations between soluble urokinase plasminogen activator receptor and established markers of cardiotoxicity in breast cancer patients receiving doxorubicin.
METHODS
We conducted a prospective cohort study of women with newly diagnosed breast cancer receiving standard-dose doxorubicin (240 mg/m) at Rush University Medical Center and Rush Oak Park Hospital (Chicago, IL) between January 2017 and May 2019. Left ventricular ejection fraction, global longitudinal strain, and cardiac biomarkers (N-terminal prohormone B-type natriuretic peptide, troponin-I, and high-sensitivity C-reactive protein) were measured at baseline and at intervals up to 12-month follow-up after end of treatment. The associations between soluble urokinase plasminogen activator receptor and these endpoints were evaluated using multivariable mixed effects linear regression.
RESULTS
Our study included 37 women (mean age 47.0 ± 9.3 years, 60% white) with a median baseline soluble urokinase plasminogen activator receptor level of 2.83 ng/dL. No participant developed cardiomyopathy based on serial echocardiography by one-year follow-up. The median percent change in left ventricular strain was -4.3% at 6-month follow-up and absolute changes in cardiac biomarkers were clinically insignificant. There were no significant associations between soluble urokinase plasminogen activator receptor and these markers of cardiotoxicity (all p > 0.05).
CONCLUSIONS
In this breast cancer cohort, doxorubicin treatment was associated with a very low risk for cardiotoxicity. Across this narrow range of clinical endpoints, soluble urokinase plasminogen activator receptor was not associated with markers of subclinical cardiotoxicity. Further studies are needed to clarify the prognostic utility of soluble urokinase plasminogen activator receptor in doxorubicin-associated cardiomyopathy and should include a larger cohort of leukemia and lymphoma patients who receive higher doses of doxorubicin.
背景
可溶性尿激酶型纤溶酶原激活物受体是一种炎症生物标志物，可能对心血管结局具有预后价值。我们旨在确定可溶性尿激酶型纤溶酶原激活物受体与接受多柔比星治疗的乳腺癌患者已确立的心脏毒性标志物之间的关联。
方法
我们对2017年1月至2019年5月期间在拉什大学医学中心和拉什橡树园医院（伊利诺伊州芝加哥）接受标准剂量多柔比星（240mg/m）治疗的新诊断乳腺癌女性进行了一项前瞻性队列研究。在基线时以及治疗结束后长达12个月的随访期间定期测量左心室射血分数、整体纵向应变和心脏生物标志物（N末端B型利钠肽原、肌钙蛋白I和高敏C反应蛋白）。使用多变量混合效应线性回归评估可溶性尿激酶型纤溶酶原激活物受体与这些终点之间的关联。
结果
我们的研究纳入了37名女性（平均年龄47.0±9.3岁，60%为白人），基线可溶性尿激酶型纤溶酶原激活物受体水平中位数为2.83ng/dL。通过一年的随访，基于系列超声心动图，没有参与者发生心肌病。在6个月的随访中，左心室应变的中位数变化百分比为-4.3%，心脏生物标志物的绝对变化在临床上无显著意义。可溶性尿激酶型纤溶酶原激活物受体与这些心脏毒性标志物之间无显著关联（所有p>0.05）。
结论
在这个乳腺癌队列中，多柔比星治疗与极低的心脏毒性风险相关。在这个狭窄的临床终点范围内，可溶性尿激酶型纤溶酶原激活物受体与亚临床心脏毒性标志物无关。需要进一步的研究来阐明可溶性尿激酶型纤溶酶原激活物受体在多柔比星相关心肌病中的预后价值，并且应该纳入更大规模的接受更高剂量多柔比星治疗的白血病和淋巴瘤患者队列。
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