Department of Cardiovascular Medicine, Faculty of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Clin Res Cardiol. 2019 Oct;108(10):1128-1139. doi: 10.1007/s00392-019-01448-4. Epub 2019 Mar 11.
Trastuzumab-related cardiotoxicity (TRC) has been considered as reversible. However, recent studies have raised concern against reversibility of left ventricular (LV) systolic dysfunction in breast cancer patients treated with trastuzumab. In addition, the efficacy of medical treatment for heart failure (HF) including renin-angiotensin inhibitors and β-blockers has not been defined in TRC.
We retrospectively studied 160 patients with breast cancer receiving trastuzumab in the adjuvant (n = 129) as well as metastatic (n = 31) settings in our institution from 2006 to 2015. During the median follow-up of 3.5 years, 20 patients (15.5%) receiving adjuvant trastuzumab and 7 patients (22.6%) with metastatic breast cancer developed TRC with a mean decrease in LV ejection fraction (EF) of 19.8%. By the multivariate analysis, lower LVEF before trastuzumab (OR 1.30; 95% CI 1.16-1.48; P = 0.0001) independently predicted subsequent development of TRC. LV systolic dysfunction was reversible in 20 patients (74.1%) with a median time to recovery of 7 months, which was independently associated with lower dose of anthracyclines (OR 1.03; 95% CI 1.01-1.07, P = 0.020) and an introduction of renin-angiotensin inhibitors and β-blockers (OR 19.0; 95% CI 1.00-592.2, P = 0.034).
Irreversible decline in LVEF occurred in patients who underwent trastuzumab in combination with anthracyclines with a relatively high frequency. The lower cumulative dose of anthracyclines and HF treatment including renin-angiotensin inhibitors and β-blockers were both independent predictors to enhance LV functional reversibility in patients with TRC.
曲妥珠单抗相关性心脏毒性（TRC）被认为是可逆的。然而，最近的研究对曲妥珠单抗治疗的乳腺癌患者左心室（LV）收缩功能障碍的可逆性提出了质疑。此外，在 TRC 中，包括肾素-血管紧张素抑制剂和β受体阻滞剂在内的心力衰竭（HF）药物治疗的疗效尚未确定。
我们回顾性研究了 2006 年至 2015 年期间在我院接受曲妥珠单抗辅助治疗（n=129）和转移性（n=31）治疗的 160 例乳腺癌患者。在中位 3.5 年的随访期间，接受辅助曲妥珠单抗治疗的 20 例患者（15.5%）和转移性乳腺癌的 7 例患者（22.6%）发生 TRC，LV 射血分数（EF）平均下降 19.8%。多变量分析显示，曲妥珠单抗治疗前较低的 LVEF（OR 1.30；95%CI 1.16-1.48；P=0.0001）可独立预测 TRC 的发生。20 例（74.1%）LV 收缩功能障碍患者的 LV 收缩功能障碍是可逆的，中位恢复时间为 7 个月，与较低的蒽环类药物剂量（OR 1.03；95%CI 1.01-1.07，P=0.020）和肾素-血管紧张素抑制剂和β受体阻滞剂的应用（OR 19.0；95%CI 1.00-592.2，P=0.034）独立相关。
接受曲妥珠单抗联合蒽环类药物治疗的患者 LVEF 下降呈不可逆趋势，且频率较高。蒽环类药物累积剂量较低，HF 治疗包括肾素-血管紧张素抑制剂和β受体阻滞剂，是改善 TRC 患者 LV 功能可逆性的独立预测因素。
