新诊断乳腺癌妇女血管功能的变化及其与心脏毒性的相关性

A. Hazim, Lara F Nhola, Vidur Kailash, Song Zhang, Nicole P. Sandhu, Amir Lerman, C. Loprinzi, K. Ruddy, H. Villarraga, Bradley Lewis, Joerg Herrmann
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摘要

本研究的目的是评估her2定向治疗(HER2-Tx)对外周血管反应性的影响及其与心功能变化的相关性,以及蒽环类药物/环磷酰胺(AC)治疗的叠加效应和基线心血管风险。新诊断为1-3期her2阳性乳腺癌的女性接受HER2-Tx +/- AC的单中心前瞻性队列研究。所有参与者接受基线和3个月的外周动脉压测仪(endodo - pat)、血管生物标志物(c型利钠肽(CNP)和神经调节蛋白-1β (NRG-1β)和超声心动图评估。心脏毒性定义为左心室射血分数(LVEF)下降>10%至<53%。在纳入的47例患者中,20例(43%)在接受HER2-Tx治疗的同时接受了AC治疗。在接受HER-Tx联合AC治疗的患者中,Endo-PAT反应性充血指数(RHI)恶化≥20%的情况比单独接受HER2-Tx治疗的患者更常见(65% vs 22%;p = 0.003)。CNP和log NRG-1β水平降低1个标准差在AC组和非AC组之间无显著差异(CNP: 20.0% vs 7.4%;p=0.20, NRG-1β: 15% vs 11%;p=0.69), GLS也没有(35% vs 37%;p = 0.89)。早在接触AC后3个月,接受AC治疗的患者的3D GE LVEF就显著低于未接受AC治疗的患者(平均59.3% (SD 3) vs. 63.8 (SD 4);p = 0.02)。RHI和GLS是唯一与LVEF变化相关的参数。与AC联合治疗,而不是单独使用HER2-Tx,会导致周围血管和心脏功能下降。更大规模的研究需要更精确地定义癌症患者血管和心脏功能变化之间的因果关系。
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Changes in Vascular Function and Correlation with Cardiotoxicity in Women with Newly Diagnosed Breast Cancer
The objective of this study was to assess the effect of HER2-directed therapy (HER2-Tx) on peripheral vasoreactivity and its correlation with cardiac function changes and the additive effects of anthracycline/cyclophosphamide (AC) therapy and baseline cardiovascular risk. Single-center, prospective cohort study of women with newly diagnosed stage 1-3 HER2-positive breast cancer undergoing HER2-Tx +/- AC. All participants underwent baseline and three-monthly evaluations with Endo-Peripheral Arterial Tonometry (Endo-PAT), vascular biomarkers (C-type natriuretic peptide (CNP) and neuregulin-1 beta (NRG-1β)), and echocardiography. Cardiotoxicity was defined as a decrease in the left ventricular ejection fraction (LVEF) of >10% to a value <53%. Of the 47 patients enrolled, 20 (43%) received AC in addition to HER2-Tx. Deterioration of reactive hyperemia index (RHI) on Endo-PAT by ≥20% was more common in patients receiving HER-Tx plus AC than HER2-Tx alone (65% vs 22%; p=0.003). A decrease in CNP and log NRG-1β levels by 1 standard deviation did not differ significantly between the AC and non-AC groups (CNP: 20.0% vs 7.4%; p=0.20 and NRG-1β: 15% vs 11%; p=0.69) nor did GLS (35% vs 37%; p=0.89). Patients treated with AC had a significantly lower 3D GE LVEF than non-AC recipients as early as 3 months after exposure (mean 59.3 % (SD 3) vs. 63.8 (SD 4); p=0.02). RHI and GLS were the only parameters correlating with LVEF change. Combination therapy with AC, but not HER2-Tx alone, leads to a decline in peripheral vascular and cardiac function. Larger studies will need to define more precisely the causal correlation between vascular and cardiac function changes in cancer patients.
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