Lynce Filipa, Barac Ana, Tan Ming T, Asch Federico M, Smith Karen L, Dang Chau, Isaacs Claudine, Swain Sandra M
Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, D.C., USA.
MedStar Washington Hospital Center, Washington, D.C., USA.
Oncologist. 2017 May;22(5):518-525. doi: 10.1634/theoncologist.2016-0412. Epub 2017 Mar 17.
Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. Current U.S. Food and Drug Administration recommendations limit the use of HER2 targeted agents to patients with normal left ventricular (LV) systolic function.
The objective of the SAFE-HEaRt study is to evaluate the cardiac safety of HER2 targeted therapy in patients with HER2 positive breast cancer and mildly reduced left ventricular ejection fraction (LVEF) with optimized cardiac therapy. Thirty patients with histologically confirmed HER2 positive breast cancer (stage I-IV) and reduced LVEF (40% to 49%) who plan to receive HER2 targeted therapy for ≥3 months will be enrolled. Prior to initiation on study, optimization of heart function with beta-blockers and angiotensin converting enzyme inhibitors will be initiated. Patients will be followed by serial echocardiograms and cardiac visits during and 6 months after completion of HER2 targeted therapy. Myocardial strain and blood biomarkers, including cardiac troponin I and high-sensitivity cardiac troponin T, will be examined at baseline and during the study.
LV dysfunction in patients with breast cancer poses cardiac and oncological challenges and limits the use of HER2 targeted therapies and its oncological benefits. Strategies to prevent cardiac dysfunction associated with HER2 targeted therapy have been limited to patients with normal LVEF, thus excluding patients who may receive the highest benefit from those strategies. SAFE-HEaRt is the first prospective pilot study of HER2 targeted therapies in patients with reduced LV function while on optimized cardiac treatment that can provide the basis for clinical practice changes. 2017;22:518-525 IMPLICATIONS FOR PRACTICE: Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. To our knowledge, SAFE-HEaRt is the first clinical trial that prospectively tests the hypothesis that HER2 targeted therapies may be safely administered in patients with mildly reduced cardiac function in the setting of ongoing cardiac treatment and monitoring. The results of this study will provide cardiac safety data and inform consideration of clinical practice changes in patients with HER2 positive breast cancer and reduced cardiac function, as well as provide information regarding cardiovascular monitoring and treatment in this population.
人表皮生长因子受体2（HER2）靶向治疗对HER2阳性乳腺癌的辅助治疗及转移治疗具有生存获益，但与心脏功能障碍相关。美国食品药品监督管理局目前的建议将HER2靶向药物的使用限制在左心室（LV）收缩功能正常的患者。
SAFE-HEaRt研究的目的是评估HER2靶向治疗对HER2阳性乳腺癌且左心室射血分数（LVEF）轻度降低并接受优化心脏治疗患者的心脏安全性。将纳入30例组织学确诊为HER2阳性乳腺癌（I-IV期）且LVEF降低（40%至49%）、计划接受HER2靶向治疗≥3个月的患者。在开始研究前，将启动使用β受体阻滞剂和血管紧张素转换酶抑制剂优化心脏功能。在HER2靶向治疗期间及治疗完成后6个月，通过系列超声心动图和心脏检查对患者进行随访。将在基线及研究期间检测心肌应变和血液生物标志物，包括心肌肌钙蛋白I和高敏心肌肌钙蛋白T。
乳腺癌患者的左心室功能障碍带来了心脏和肿瘤学方面的挑战，并限制了HER2靶向治疗的使用及其肿瘤学获益。预防与HER2靶向治疗相关的心脏功能障碍的策略仅限于LVEF正常的患者，从而排除了可能从这些策略中获得最大获益的患者。SAFE-HEaRt是第一项针对左心室功能降低且接受优化心脏治疗的患者进行HER2靶向治疗的前瞻性初步研究，可为临床实践的改变提供依据。2017年；22:518 - 525对实践的启示：人表皮生长因子受体2（HER2）靶向治疗对HER2阳性乳腺癌的辅助治疗及转移治疗具有生存获益，但与心脏功能障碍相关。据我们所知，SAFE-HEaRt是第一项前瞻性检验以下假设的临床试验：在持续进行心脏治疗和监测的情况下，HER2靶向治疗可安全地应用于心脏功能轻度降低的患者。本研究结果将提供心脏安全性数据，并为考虑改变HER2阳性乳腺癌且心脏功能降低患者的临床实践提供信息，同时也将提供该人群心血管监测和治疗的相关信息。
