BACKGROUND Dose-dense (DD) adjuvant chemotherapy improves outcomes in early breast cancer (BC). However, there are no phase 3 randomized data to inform on its combination with trastuzumab for patients with human epidermal growth factor receptor 2 (HER2)-positive disease. METHODS This was a protocol-predefined secondary analysis of the randomized phase 3 Pan-European Tailored Chemotherapy (PANTHER) trial. Women 65 years old or younger with node-positive or high-risk, node-negative BC were randomized 1:1 to either tailored (according to hematologic nadirs) and DD epirubicin and cyclophosphamide followed by docetaxel or standard 5-fluorouracil, epirubicin, and cyclophosphamide plus docetaxel every 3 weeks. Patients with HER2-positive disease received 1 year of adjuvant trastuzumab. The primary endpoint was BC relapse-free survival. In addition, HER2-positive patients and an equal number of HER2-negative patients matched for age, treatment group, and institution who were enrolled at Swedish sites were asked to participate in a predefined study of cardiac safety and underwent echocardiography or multigated acquisition scanning and electrocardiography at the baseline and at 4 and 6 years of follow-up. RESULTS There were 342 HER2-positive patients; 335 received at least 1 dose of trastuzumab, and 29 patients discontinued trastuzumab prematurely. Relapse-free survival was not statistically significantly in favor of the tailored and DD group (hazard ratio, 0.68; 95% confidence interval, 0.37-1.27; P = .231). Cardiac outcomes after 4 and 6 years of follow-up did not differ significantly between HER2-positive and HER2-negative patients or between the 2 treatment groups. CONCLUSIONS The combination of DD chemotherapy and trastuzumab decreased the relative risk for relapse by 32% in comparison with standard treatment, a statistically nonsignificant difference. Its efficacy and safety merit further evaluation as part of both escalation and de-escalation strategies.

中文翻译：

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量身定制且剂量密集的辅助化疗和曲妥珠单抗对切除的HER2阳性乳腺癌的疗效和安全性：PANTHER 3期试验的结果。

背景技术剂量密集（DD）辅助化疗可改善早期乳腺癌（BC）的预后。但是，尚无3期随机数据来说明其与曲妥珠单抗联合用于人表皮生长因子受体2（HER2）阳性疾病的患者。方法这是对方案3泛欧洲量身定制的化学治疗（PANTHER）试验进行方案预定义的二次分析。65岁或以下的淋巴结阳性或高风险，淋巴结阴性的BC女性按1：1比例随机分配（根据血液学最低点）和DD表柔比星和环磷酰胺，然后使用多西紫杉醇或标准的5-氟尿嘧啶，表柔比星和每3周加一次环磷酰胺加多西他赛。HER2阳性患者接受1年曲妥珠单抗辅助治疗。主要终点为BC无复发生存期。此外，要求在瑞典研究中心就诊的年龄，治疗组和机构相匹配的HER2阳性患者和相等数量的HER2阴性患者参加心脏研究的既定研究，并在医院接受超声心动图或多路采集扫描和心电图检查基线以及随访的4年和6年。结果342例HER2阳性患者。335名患者接受了至少1剂曲妥珠单抗治疗，其中29例患者过早停用了曲妥珠单抗。无复发生存率在统计学上没有明显地偏向于特效组和DD组（危险比，0.68； 95％置信区间，0.37-1.27； P = .231）。在HER2阳性和HER2阴性的患者之间或在2个治疗组之间，随访4年和6年后的心脏结局无显着差异。结论与标准治疗相比，DD化疗和曲妥珠单抗的组合使复发的相对风险降低了32％，差异无统计学意义。作为升级和降级策略的一部分，其有效性和安全性值得进一步评估。