本研究旨在全面探讨PIK3CA基因突变对接受抗HER2治疗的HER2阳性乳腺癌的临床意义。我们系统地搜索了PubMed、Embase和Cochrane数据库中的相关研究，评估了PIK3CA基因突变与接受抗HER2治疗的HER2阳性乳腺癌患者的预后之间的关联。主要结局包括：（1）新辅助治疗中的病理学完全缓解（pCR）或无病生存期（DFS）；（2）辅助治疗中的DFS或侵袭性DFS；（3）转移治疗中的客观缓解率（ORR）、无进展生存期（PFS）、进展时间（TTP）或总生存期（OS）。根据TCGA乳腺癌数据集，基于PIK3CA基因突变状态，检查了HER2阳性乳腺癌的突变景观。总共鉴定到43项符合条件的研究，涵盖了11,099名具有PIK3CA基因突变状态可用数据的患者。在新辅助治疗中，PIK3CA基因突变与较低的pCR率显著相关（OR=0.23，95% CI 0.19-0.27，p<0.001）。无论是单药还是双药抗HER2治疗以及激素受体状态如何，该关联都仍然显著。在新辅助治疗或辅助治疗中，PIK3CA基因突变与DFS之间没有显著差异。在转移治疗中，PIK3CA基因突变预示着较差的ORR（OR=0.26，95%CI 0.17-0.40，p<0.001）、较差的PFS（HR=1.28，95%CI 1.03-1.59，p=0.024）和较差的TTP（HR=2.27，95%CI 1.54-3.34，p<0.001）。然而，PIK3CA基因突变状态与总生存期之间没有显著关联。在HER2阳性乳腺癌中，具有PIK3CA基因突变和野生型PIK3CA的个体间观察到不同的突变景观。在新辅助接受抗HER2治疗的HER2阳性乳腺癌中，PIK3CA基因突变与较低的pCR率显著相关。在转移治疗中，PIK3CA基因突变预示着较差的ORR、PFS和TTP。这些结果提示了将PI3K抑制剂作为这些患者的治疗选择的潜力。版权所有©2023. Elsevier Inc. 发布。

This study aimed to comprehensively explore the clinical significance of PIK3CA mutation in human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with anti-HER2 therapy.We systematically searched PubMed, Embase, and the Cochrane databases for eligible studies assessing the association between PIK3CA mutation and outcomes in patients with HER2-positive breast cancer receiving anti-HER2 therapy. The main outcomes included: (1) pathological complete response (pCR) or disease-free survival (DFS) for the neoadjuvant setting; (2) DFS or invasive DFS for the adjuvant setting; (3) objective response rate (ORR), progression-free survival (PFS), time-to-progression (TTP), or overall survival (OS) for the metastatic setting. The mutational landscape of HER2-positive breast cancer according to PIK3CA mutation status was examined based on TCGA breast cancer dataset.Totally, 43 eligible studies, covering 11,099 patients with available data on PIK3CA mutation status, were identified. In the neoadjuvant setting, PIK3CA mutation was significantly associated with a lower pCR rate (OR=0.23, 95% CI 0.19-0.27, p<0.001). This association remained significant irrespective of the type of anti-HER2 therapy (single-agent or dual-agent) and hormone receptor status. There were no significant differences in DFS between PIK3CA mutated and wild-type patients in either the neoadjuvant or adjuvant settings. In the metastatic setting, PIK3CA mutation predicted worse ORR (OR=0.26, 95%CI 0.17-0.40, p<0.001), PFS (HR=1.28, 95%CI 1.03-1.59, p = 0.024) and TTP (HR=2.27, 95%CI 1.54-3.34, p<0.001). However, no significant association was observed between PIK3CA mutation status and OS. Distinct mutational landscapes were observed in HER2-positive breast cancer between individuals with PIK3CA mutations and those with wild-type PIK3CA.PIK3CA mutation was significantly associated with a lower pCR rate in HER2-positive breast cancer treated with neoadjuvant anti-HER2 therapy. In the metastatic setting, PIK3CA mutation was predictive of worse ORR, PFS and TTP. These results suggest the potential for developing PI3K inhibitors as a therapeutic option for these patients.Copyright © 2023. Published by Elsevier Inc.