PURPOSE Anthracyclines are frequently used in adjuvant treatment for early-stage breast cancer (ESBC). The purpose of this study was to evaluate cardiotoxic effects in the first five years after treatment with different anthracycline-based regimens. METHODS CCTG MA.21 (NCT000142) was a phase III trial in ESBC that compared cyclophosphamide (75 mg/m2) orally for 14 days, epirubicin (60 mg/m2) and fluorouracil, IV days one and eight (CEF) for six cycles; dose-dense epirubicin (120 mg/m2) and cyclophosphamide, IV every 2 weeks for six cycles with concurrent G-CSF then paclitaxel every 2 weeks for four cycles (ddEC/T); doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks for four cycles then four cycles q3 weekly paclitaxel (175 mg/m2) (AC/T). ENDPOINTS LVEF decline; LV function changes (heart failure), or Grade 3-4 cardiac ischemia/infarction. A competing risk analysis was performed with endpoints of cardiotoxicity or recurrence in first 5 years after completion of chemotherapy. RESULTS 2104 women were randomized. Compliance with cardiac LVEF assessments was 70% at 5 years in all arms. The 5-year cumulative risks of any cardiac event for CEF, ddECT, and AC/T were 22.3% (95%CI 18.9 to 25.7), 14.2% (95%CI 11.0 to 17.3), and 8.1% (95%CI 5.8 to 10.4), respectively, p < 0.0001. At 5 years, women in the ddEC/T and AC/T group had significantly lower risk of cardiotoxicity than those given CEF (HR 0.599 and 0.371, respectively). Most events were asymptomatic drop in LVEF. CONCLUSIONS Asymptomatic changes in LVEF accounted for most of the cardiotoxicity. The majority of cardiac events occurred in year one although occurrence of cardiotoxicity over time highlights the need for improved risk stratification to guide cardiac surveillance strategies.

中文翻译：

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蒽环类药物对早期乳腺癌患者的心脏毒性：加拿大癌症试验组 (CCTG) MA.21 的经验。

用途 蒽环类药物经常用于早期乳腺癌 (ESBC) 的辅助治疗。本研究的目的是评估不同蒽环类药物治疗后前五年的心脏毒性作用。方法 CCTG MA.21 (NCT000142) 是 ESBC 的 III 期试验，比较环磷酰胺 (75 mg/m2) 口服 14 天、表柔比星 (60 mg/m2) 和氟尿嘧啶、IV 天第一天和第八天 (CEF) 六个周期; 剂量密集的表柔比星 (120 mg/m2) 和环磷酰胺，每 2 周 IV 一次，共 6 个周期，同时使用 G-CSF，然后每 2 周紫杉醇，共 4 个周期 (ddEC/T)；多柔比星 (60 mg/m2) 和环磷酰胺 (600 mg/m2) 每 3 周一次，共 4 个周期，然后 4 个周期 q3 每周一次紫杉醇 (175 mg/m2) (AC/T)。端点 LVEF 下降；LV 功能改变（心力衰竭），或 3-4 级心脏缺血/梗塞。在化疗完成后的前 5 年内，对心脏毒性或复发的终点进行了竞争风险分析。结果 2104 名女性被随机分配。5 年时，所有组对心脏 LVEF 评估的依从性为 70%。CEF、ddECT 和 AC/T 的任何心脏事件的 5 年累积风险分别为 22.3%（95%CI 18.9 至 25.7）、14.2%（95%CI 11.0 至 17.3）和 8.1%（95%CI 5.8）至 10.4)，分别为 p < 0.0001。5 年时，ddEC/T 和 AC/T 组的女性心脏毒性风险显着低于 CEF 组（HR 分别为 0.599 和 0.371）。大多数事件是无症状的 LVEF 下降。结论 LVEF 的无症状变化是造成心脏毒性的主要原因。