Hazim Antonious, Nhola Lara F, Kailash Vidur, Zhang Song, Sandhu Nicole P, Lerman Amir, Loprinzi Charles L, Ruddy Kathryn J, Villarraga Hector R, Lewis Bradley, Herrmann Joerg
Department of Oncology, Mayo Clinic, Rochester, MN, USA.
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
Eur Heart J Open. 2023 Dec 8;4(1):oead130. doi: 10.1093/ehjopen/oead130. eCollection 2024 Jan.
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-centre, prospective cohort study of women with newly diagnosed stage 1-3 HER2-positive breast cancer undergoing HER2-Tx +/- AC. All participants underwent baseline and 3-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 hyperaemia index (RHI) on Endo-PAT by ≥20% was more common in patients receiving HER-Tx plus AC than HER2-Tx alone (65% vs. 22%; = 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%; = 0.20 and NRG-1β: 15% vs. 11%; = 0.69) nor did GLS (35% vs. 37%; = 0.89). Patients treated with AC had a significantly lower 3D LVEF than non-AC recipients as early as 3 months after exposure (mean 59.3% (SD 3) vs. 63.8% (SD 4); = 0.02). Reactive hyperaemia index 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.
本研究的目的是评估HER2靶向治疗（HER2-Tx）对外周血管反应性的影响及其与心脏功能变化的相关性，以及蒽环类/环磷酰胺（AC）治疗的叠加效应和基线心血管风险。
对新诊断为1-3期HER2阳性乳腺癌且正在接受HER2-Tx±AC治疗的女性进行单中心前瞻性队列研究。所有参与者均接受了使用外周动脉张力测量法（Endo-PAT）、血管生物标志物[C型利钠肽（CNP）和神经调节蛋白-1β（NRG-1β）]以及超声心动图进行的基线和每3个月一次的评估。心脏毒性定义为左心室射血分数（LVEF）降低>10%，降至<53%。在纳入的47例患者中，20例（43%）除接受HER2-Tx外还接受了AC治疗。接受HER-Tx加AC治疗的患者中，Endo-PAT上反应性充血指数（RHI）恶化≥20%的情况比仅接受HER2-Tx治疗的患者更常见（65%对22%；P = 0.003）。AC组和非AC组之间，CNP和log NRG-1β水平降低1个标准差并无显著差异（CNP：20.0%对7.4%；P = 0.20，NRG-1β：15%对11%；P = 0.69），整体纵向应变（GLS）也无显著差异（35%对37%；P = 0.89）。接受AC治疗的患者在暴露后仅3个月时，其三维LVEF就显著低于未接受AC治疗的患者（平均59.3%（标准差3）对63.8%（标准差4）；P = 0.02）。反应性充血指数和GLS是与LVEF变化相关的唯一参数。
AC联合治疗而非单独的HER2-Tx会导致外周血管和心脏功能下降。需要更大规模的研究来更精确地确定癌症患者血管和心脏功能变化之间的因果关系。
