曲妥珠单抗会增加乳腺癌患者心脏事件（CEs）的发生率。联合应用珀珠单抗（P）和曲妥珠单抗（T）可改善高危人类表皮生长因子受体2（HER2）阳性早期乳腺癌（BC）的疗效，并已成为标准治疗。我们在APHINITY Ⅲ期试验中分析了P和T的心脏安全性。研究入组要求左室射血分数（LVEF）≥55％。治疗期间每3个月进行LVEF评估，每6个月评估直至36个月，每年评估直至10年。主要CE定义为心力衰竭III / IV级和LVEF明显下降（定义为从基线至<50％的下降≥10％）或心脏死亡。次要CE定义为确认的LVEF明显下降或经心脏咨询委员会确认的CE。安全性分析人口包括4769名患者。随访中位数为74个月，159名患者（3.3％）出现CEs：P + T组83名（3.5％），T组76名（3.2％）。大多数CEs发生在抗HER2治疗期间（123例；77.4％），其中133例（83.6％）为无症状或轻度症状的LVEF下降。每组均有2例心脏死亡（0.1％）。心脏风险因素包括年龄> 65岁，体重指数≥25 kg / m2，基线LVEF介于55％和<60％之间以及使用含蒽环类化疗方案。根据随后的LVEF值观察到127/155名患者（81.9％）出现的急性康复。与T单独相比，使用P + T联合治疗不会增加CEs的风险。使用蒽环类化疗增加CEs的风险，故可考虑非蒽环类化疗，尤其是有心血管风险因素的患者。版权所有©2022作者。由Elsevier出版发行。保留所有权利。

Trastuzumab increases the incidence of cardiac events (CEs) in patients with breast cancer (BC). Dual blockade with pertuzumab (P) and trastuzumab (T) improves BC outcomes and is the standard of care for high-risk human epidermal growth factor receptor 2 (HER2)-positive early BC patients. We analyzed the cardiac safety of P and T in the phase III APHINITY trial.Left ventricular ejection fraction (LVEF) ≥ 55% was required at study entry. LVEF assessment was carried out every 3 months during treatment, every 6 months up to month 36, and yearly up to 10 years. Primary CE was defined as heart failure class III/IV and a significant decrease in LVEF (defined as ≥10% from baseline and to <50%), or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF, or CEs confirmed by the cardiac advisory board.The safety analysis population consisted of 4769 patients. With 74 months of median follow-up, CEs were observed in 159 patients (3.3%): 83 (3.5%) in P + T and 76 (3.2%) in T arms, respectively. Most CEs occurred during anti-HER2 therapy (123; 77.4%) and were asymptomatic or mildly symptomatic decreases in LVEF (133; 83.6%). There were two cardiac deaths in each arm (0.1%). Cardiac risk factors indicated were age > 65 years, body mass index ≥ 25 kg/m2, baseline LVEF between 55% and <60%, and use of an anthracycline-containing chemotherapy regimen. Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 patients (81.9%).Dual blockade with P + T does not increase the risk of CEs compared with T alone. The use of anthracycline-based chemotherapy increases the risk of a CE; hence, non-anthracycline chemotherapy may be considered, particularly in patients with cardiovascular risk factors.Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.