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对心功能正常的乳腺癌女性患者接受曲妥珠单抗治疗时心脏生物标志物的探索性分析。

Exploratory analysis of cardiac biomarkers in women with normal cardiac function receiving trastuzumab for breast cancer.

作者信息

Goel Shom, Simes R John, Beith Jane M

机构信息

Sydney Cancer Centre, Royal Prince Alfred Hospital, New South Wales, Australia.

出版信息

Asia Pac J Clin Oncol. 2011 Sep;7(3):276-80. doi: 10.1111/j.1743-7563.2011.01422.x.

Abstract

AIM

As there is no method to detect trastuzumab-related cardiotoxicity (TRC) preclinically, patients are monitored with serial assessments of left ventricular ejection fraction (LVEF) with instigation of cardiac therapy and possible interruption of trastuzumab therapy if TRC develops. Serum cardiac biomarkers, including troponins and natriuretic peptides, represent possible tools to detect cardiotoxicity at a preclinical level.

METHODS

We sought biochemical evidence of cardiac damage or strain in a cohort of women already receiving trastuzumab by performing a cross-sectional study of serum cardiac biomarkers. All patients had a normal LVEF and no clinical evidence of cardiac failure. Serum troponin I and N-terminal pro-B type natriuretic peptide (NT pro-BNP) were assayed immediately prior to trastuzumab infusion (t0; n = 36) and 24 hours later (t24; n = 31).

RESULTS

Troponin I was not elevated in any patient at t0 or t24. Overall 14/36 (39%) patients had at least one NT pro-BNP level above the upper limit of normal (ULN) and both levels were above the ULN in 8/31 (26%) patients. There was no significant change in NT pro-BNP from t0 to t24.

CONCLUSION

NT pro-BNP levels are elevated in a significant proportion of patients with normal LVEF receiving trastuzumab. Troponin I levels are not raised in this group, perhaps reflecting the mechanism of cardiotoxicity. The data provide biochemical evidence of subclinical cardiac strain in women receiving trastuzumab. Results are exploratory and have informed the design of a larger study examining the predictive utility of serial serum NT pro-BNP levels for TRC in the adjuvant setting.

摘要

目的

由于临床前没有检测曲妥珠单抗相关心脏毒性(TRC)的方法,因此通过连续评估左心室射血分数(LVEF)对患者进行监测,若发生TRC则启动心脏治疗并可能中断曲妥珠单抗治疗。血清心脏生物标志物,包括肌钙蛋白和利钠肽,是在临床前水平检测心脏毒性的可能工具。

方法

我们通过对血清心脏生物标志物进行横断面研究,在一组已经接受曲妥珠单抗治疗的女性中寻找心脏损伤或应激的生化证据。所有患者的LVEF均正常,且无心力衰竭的临床证据。在曲妥珠单抗输注前(t0;n = 36)和24小时后(t24;n = 31)立即检测血清肌钙蛋白I和N末端B型利钠肽原(NT pro-BNP)。

结果

在t0或t24时,没有患者的肌钙蛋白I升高。总体而言,14/36(39%)的患者至少有一次NT pro-BNP水平高于正常上限(ULN),8/31(26%)的患者两个时间点的水平均高于ULN。从t0到t24,NT pro-BNP没有显著变化。

结论

在LVEF正常的接受曲妥珠单抗治疗的患者中,相当一部分患者的NT pro-BNP水平升高。该组患者的肌钙蛋白I水平没有升高,这可能反映了心脏毒性的机制。这些数据为接受曲妥珠单抗治疗的女性亚临床心脏应激提供了生化证据。结果是探索性的,并为一项更大规模的研究设计提供了信息,该研究旨在探讨在辅助治疗中连续检测血清NT pro-BNP水平对TRC的预测效用。

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