Chen Siyi, Yang Zitong, Sun Jiahong, Si Huiyan, Xu Hu, Li Qingyang, Guo Shiqi, Xue Yuanbo, Zhu Li, Wang Jiandong
Medical School of Chinese PLA, Beijing, China.
Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
Gland Surg. 2025 Jun 30;14(6):1079-1090. doi: 10.21037/gs-2025-25. Epub 2025 Jun 26.
Human epidermal growth factor receptor 2 (HER2) positive breast cancer is a distinct molecular subtype. Trastuzumab-based neoadjuvant therapy (NAT) (combined with chemotherapy and/or additional anti-HER2 agents) is the standard of care, but the optimal duration of trastuzumab cycles (short-term: <6 long-term: ≥6) remains controversial. This meta-analysis aims to comprehensively evaluate the efficacy and safety of long-term (≥6 cycles) and short-term (<6 cycles) neoadjuvant trastuzumab treatment for HER2-positive breast cancer.
The PubMed, EMBASE, and Web of Science databases were systematically searched to include randomized controlled trials (RCTs) comparing long-term and short-term neoadjuvant trastuzumab treatment for HER2 positive breast cancer. The primary outcome measurement was the pathological complete response (pCR) rate, and the secondary outcome measurement was the incidence of adverse events. RevMan and STATA software were used for meta-analysis.
A total of five RCTs involving 799 patients were included. The meta-analysis showed that there was no significant difference in pCR between long-term and short-term treatment [risk ratio (RR) =0.78, 95% confidence interval (CI): 0.60-1.02; P=0.07; I=62%], but long-term treatment had a higher trend in pCR. After excluding the Z1041 trial with high heterogeneity, the pCR of long-term treatment was significantly better than that of short-term treatment (RR =0.69, 95% CI: 0.50-0.95; P=0.02; I=50%). The incidence of grade 3 and above adverse events in short-term treatment was significantly lower than that in long-term treatment (RR =0.75, 95% CI: 0.59-0.96; P=0.02; I=0%). Subgroup analysis showed that in single anti-HER2 therapy, after excluding Z1041, the pCR of long-term treatment was better than that of short-term treatment (RR =0.61, 95% CI: 0.45-0.84; P=0.002; I=0%); in the hormone receptor positive (HR+) group, after excluding Z1041, the pCR of long-term treatment was significantly better than that of shor-term treatment (RR =0.45, 95% CI: 0.24-0.83; P=0.01; I=2%).
This meta-analysis indicates that when using single anti-HER2 therapy (trastuzumab + chemotherapy without additional anti-HER2 agents) for neoadjuvant treatment, a long-term treatment may bring better efficacy. In dual anti-HER2 therapy, the efficacy of long- and short-term treatments is similar, and a shorter treatment cycle can be considered to reduce adverse events.
人表皮生长因子受体2（HER2）阳性乳腺癌是一种独特的分子亚型。基于曲妥珠单抗的新辅助治疗（NAT）（联合化疗和/或其他抗HER2药物）是标准治疗方案，但曲妥珠单抗治疗周期的最佳时长（短期：<6个周期；长期：≥6个周期）仍存在争议。本荟萃分析旨在全面评估长期（≥6个周期）和短期（<6个周期）新辅助曲妥珠单抗治疗HER2阳性乳腺癌的疗效和安全性。
系统检索PubMed、EMBASE和Web of Science数据库，纳入比较长期和短期新辅助曲妥珠单抗治疗HER2阳性乳腺癌的随机对照试验（RCT）。主要结局指标为病理完全缓解（pCR）率，次要结局指标为不良事件发生率。使用RevMan和STATA软件进行荟萃分析。
共纳入5项涉及799例患者的RCT。荟萃分析显示，长期和短期治疗的pCR无显著差异[风险比（RR）=0.78，95%置信区间（CI）：0.60 - 1.02；P = 0.07；I² = 62%]，但长期治疗的pCR有更高的趋势。排除异质性高的Z1041试验后，长期治疗的pCR显著优于短期治疗（RR = 0.69，95% CI：0.50 - 0.95；P = 0.02；I² = 50%）。短期治疗中3级及以上不良事件的发生率显著低于长期治疗（RR = 0.75，95% CI：0.59 - 0.96；P = 0.02；I² = 0%）。亚组分析显示，在单药抗HER2治疗中，排除Z1041后，长期治疗的pCR优于短期治疗（RR = 0.61，95% CI：0.45 - 0.84；P = 0.002；I² = 0%）；在激素受体阳性（HR +）组中，排除Z1041后，长期治疗的pCR显著优于短期治疗（RR = 0.45，95% CI：0.24 - 0.83；P = 0.01；I² = 2%）。
本荟萃分析表明，在使用单药抗HER2治疗（曲妥珠单抗 + 化疗，无其他抗HER2药物）进行新辅助治疗时，长期治疗可能带来更好的疗效。在双药抗HER2治疗中，长期和短期治疗的疗效相似，可以考虑较短的治疗周期以减少不良事件。
