Breast Unit, Department of Medicine, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, SM2 5PT, Surrey, UK.
Cardio-Oncology Service, Royal Brompton and Harefield NHS Foundation Trust, Sydney Street, Chelsea, London, SW3 6NP, UK.
Breast Cancer Res Treat. 2021 Jul;188(1):149-163. doi: 10.1007/s10549-021-06192-w. Epub 2021 Apr 5.
Trastuzumab improves survival in patients with HER2+ early breast cancer. However, cardiotoxicity remains a concern, particularly in the curative setting, and there are limited data on its incidence outside of clinical trials. We retrospectively evaluated the cardiotoxicity rates [left ventricular ejection fraction (LVEF) decline, congestive heart failure (CHF), cardiac death or trastuzumab discontinuation] and assessed the performance of a proposed model to predict cardiotoxicity in routine clinical practice.
Patients receiving curative trastuzumab between 2011 and 2018 were identified. Demographics, treatments, assessments and toxicities were recorded. Fisher's exact test, Chi-squared and logistic regression were used.
931 patients were included in the analysis. Median age was 54 years (range 24-83) and Charlson comorbidity index 0 (0-6), with 195 patients (20.9%) aged 65 or older. 228 (24.5%) were smokers. Anthracyclines were given in 608 (65.3%). Median number of trastuzumab doses was 18 (1-18). The HFA-ICOS cardiovascular risk was low in 401 patients (43.1%), medium in 454 (48.8%), high in 70 (7.5%) and very high in 6 (0.6%). Overall, 155 (16.6%) patients experienced cardiotoxicity: LVEF decline ≥ 10% in 141 (15.1%), falling below 50% in 55 (5.9%), CHF NYHA class II in 42 (4.5%) and class III-IV in 5 (0.5%) and discontinuation due to cardiac reasons in 35 (3.8%). No deaths were observed. Cardiotoxicity rates increased with HFA-ICOS score (14.0% low, 16.7% medium, 30.3% high/very high; p = 0.002).
Cardiotoxicity was relatively common (16.6%), but symptomatic heart failure on trastuzumab was rare in our cohort. The HFA-ICOS score identifies patients at high risk of cardiotoxicity.
曲妥珠单抗可改善 HER2+早期乳腺癌患者的生存率。然而，心脏毒性仍然是一个关注点，尤其是在治愈性治疗环境中，并且临床试验之外关于其发生率的数据有限。我们回顾性评估了心脏毒性发生率（左心室射血分数 [LVEF] 下降、充血性心力衰竭 [CHF]、心脏死亡或曲妥珠单抗停药），并评估了一种用于预测常规临床实践中心脏毒性的模型的性能。
确定了 2011 年至 2018 年期间接受治愈性曲妥珠单抗治疗的患者。记录了人口统计学、治疗、评估和毒性。使用 Fisher 确切检验、卡方检验和逻辑回归。
931 例患者纳入分析。中位年龄为 54 岁（范围 24-83 岁），Charlson 合并症指数为 0（0-6），年龄在 65 岁或以上的患者有 195 例（20.9%）。228 例（24.5%）为吸烟者。608 例（65.3%）接受了蒽环类药物治疗。中位曲妥珠单抗剂量为 18（1-18）。401 例（43.1%）患者的 HFA-ICOS 心血管风险低，454 例（48.8%）患者的风险中等，70 例（7.5%）患者的风险高，6 例（0.6%）患者的风险极高。总体而言，155 例（16.6%）患者发生心脏毒性：141 例（15.1%）出现 LVEF 下降≥10%，55 例（5.9%）下降至 50%以下，42 例（4.5%）出现纽约心脏病协会 [NYHA] 心功能 II 级心力衰竭，5 例（0.5%）出现 III 级/IV 级心力衰竭，35 例（3.8%）因心脏原因停药。未观察到死亡。心脏毒性发生率随 HFA-ICOS 评分升高而增加（低风险 14.0%，中风险 16.7%，高/极高风险 30.3%；p=0.002）。
在我们的队列中，心脏毒性较为常见（16.6%），但曲妥珠单抗治疗期间出现有症状的心力衰竭较为罕见。HFA-ICOS 评分可识别出发生心脏毒性的高风险患者。
