National Surgical Adjuvant Breast and Bowel Project, East Commons Professional Building, Four Allegheny Center, 5th Floor, Pittsburgh, PA 15212, USA.
J Clin Oncol. 2012 Nov 1;30(31):3792-9. doi: 10.1200/JCO.2011.40.0010. Epub 2012 Sep 17.
Cardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care.
In National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified.
At 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab.
The late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab.
心脏功能障碍（CD）是曲妥珠单抗联合辅助化疗治疗人表皮生长因子受体 2 阳性乳腺癌的一种公认风险，尤其是当治疗方案包括蒽环类药物时。鉴于曲妥珠单抗的疗效已得到证实，持续评估心脏安全性并确定 CD 的危险因素对于优化患者护理非常重要。
在国家外科辅助乳腺和肠道项目 B-31 中，一项 III 期辅助试验中，对符合曲妥珠单抗起始治疗条件的 1830 名患者进行了 CD 评估。还评估了 CD 的恢复情况。建立了一个统计模型来估计严重充血性心力衰竭（CHF）的风险。还确定了与蒽环类药物相关的心脏功能下降相关的基线患者特征。
在 7 年的随访中，接受曲妥珠单抗治疗的 944 名患者中有 37 名（4.0%）发生了心脏事件（CE），而对照组 743 名患者中有 10 名（1.3%）。协议的每个臂中都发生了 1 例心脏相关死亡。使用患者年龄和多门控采集扫描的基线左心室射血分数（LVEF）计算的心脏风险评分与 CE 的风险具有统计学相关性。停止曲妥珠单抗后，大多数发生 CD 的患者 LVEF 恢复正常范围，尽管基线水平仍经常存在一些下降。只有 2 例 CE 发生在曲妥珠单抗开始后 2 年以上。
在多柔比星/环磷酰胺化疗后加用紫杉醇时添加曲妥珠单抗后 CHF 的迟发性发展并不常见。在该方案中给予曲妥珠单抗的风险与获益仍然强烈倾向于使用曲妥珠单抗。
