Moey Melissa Y Y, Liles Darla K, Carabello Blase A
1Department of Internal Medicine, Vidant Medical Center/East Carolina University, 2100 Stantonsburg Road, Greenville, North Carolina 27834 USA.
2Department of Hematology and Oncology, Vidant Medical Center/East Carolina University, 2100 Stantonsburg Road, Greenville, North Carolina 27834 USA.
Cardiooncology. 2019 Jul 8;5:9. doi: 10.1186/s40959-019-0043-8. eCollection 2019.
Cardiotoxicity is an adverse effect of trastuzumab (TRA) in the treatment of human epidermal growth factor 2 positive (HER2+) breast cancer. Current literature on the cardioprotective effects of agents targeted against the renin-angiotensin-aldosterone system (RAAS) and beta-blockers (BB) in TRA-treated HER2+ breast cancer patients is conflicting. We hypothesized that concurrent use of RAAS inhibitors would prevent TRA-induced cardiotoxicity (TIC).
Surveillance ejection fraction (EF) at 3-month intervals up to 36 months obtained from echocardiogram or multigated acquisition (MUGA) scans were retrospectively compared to baseline EF in TRA-treated HER2+ breast cancer patients between 2011 to 2016 at a tertiary cancer center. TIC was defined as a decrease of EF by more than 15 EF percentage points from baseline on surveillance imaging. Cardiac medications and comorbidities were compared between patients with reduced EF secondary to TIC (rEF) and patients who did not experience TIC (pEF). A published clinical risk score (CRS) was applied to the patient population with calculated sensitivity analyses to determine if the CRS could predict TIC.
Of 127 patients with TRA-treated HER2+ breast cancer, 11% developed cardiotoxicity resulting in discontinuation of TRA. Cardiotoxicity with reduced EF was seen as early as 3 months and at subsequent 3-month follow up intervals up to the 15-month follow-up. Co-existing arrhythmia, coronary artery disease (CAD), hypertension (HTN) and diabetes mellitus (DM) tended to infer an increased risk for cardiotoxicity. Patients with pEF were found to be concurrently on a RAAS inhibitor more than the rEF group (OR of 0.24, 95% CI 0.05-1.11, p 0.06). The CRS high-risk cut-off had a sensitivity of 0.17 (95% CI 0.03-0.49), specificity of 0.89 (95% CI 0.82-0.94), positive predictive value of 0.14 (95% CI 0.03-0.44) and negative predictive value of 0.91 (95% CI 0.84-0.95).
Our data suggest that the concurrent use of a RAAS inhibitors during TRA treatment may provide a protective effect against TIC and warrants further investigation. The low sensitivity and positive predictive value demonstrated that the CRS has minimal utility as a screening tool for prediction of patients at high risk for TIC. Therefore, closer surveillance of patients receiving TRA is warranted for early detection of TIC.
心脏毒性是曲妥珠单抗（TRA）治疗人表皮生长因子2阳性（HER2+）乳腺癌时的一种不良反应。目前关于靶向肾素-血管紧张素-醛固酮系统（RAAS）的药物和β受体阻滞剂（BB）对接受TRA治疗的HER2+乳腺癌患者心脏保护作用的文献存在矛盾。我们假设同时使用RAAS抑制剂可预防TRA诱导的心脏毒性（TIC）。
回顾性比较了2011年至2016年在一家三级癌症中心接受TRA治疗的HER2+乳腺癌患者，通过超声心动图或多门控采集（MUGA）扫描在长达36个月的时间里每3个月监测一次的射血分数（EF）与基线EF。TIC定义为监测成像时EF较基线下降超过15个EF百分点。比较了因TIC导致EF降低的患者（rEF）和未发生TIC的患者（pEF）的心脏药物使用情况和合并症。将一个已发表的临床风险评分（CRS）应用于该患者群体，并进行敏感性分析以确定CRS是否能预测TIC。
在127例接受TRA治疗的HER2+乳腺癌患者中，11%发生心脏毒性，导致TRA停用。EF降低的心脏毒性最早在3个月时出现，并在随后长达15个月的3个月随访间隔中均有发现。并存心律失常、冠状动脉疾病（CAD）、高血压（HTN）和糖尿病（DM）往往提示心脏毒性风险增加。发现pEF患者同时使用RAAS抑制剂的比例高于rEF组（比值比为0.24，95%可信区间为0.05-1.11，p = 0.06）。CRS高危临界值的敏感性为0.17（95%可信区间为0.03-0.49），特异性为0.89（95%可信区间为0.82-0.94），阳性预测值为0.14（95%可信区间为0.03-0.44），阴性预测值为0.91（95%可信区间为0.84-0.95）。
我们的数据表明，在TRA治疗期间同时使用RAAS抑制剂可能对TIC具有保护作用，值得进一步研究。低敏感性和阳性预测值表明CRS作为预测TIC高危患者的筛查工具效用极小。因此，有必要对接受TRA治疗的患者进行更密切的监测，以便早期发现TIC。
