乳腺癌（BC）是最常见的癌症，也是全球女性癌症相关死亡的第二大原因。尽管治疗策略取得了进步，许多患者仍然出现难以治疗的转移性疾病。肿瘤的发生和进展受到肿瘤细胞内遗传/表观遗传变化以及肿瘤微环境（TME）通过动态通讯的改变的影响。 TME 包含多种元素，包括免疫细胞、肿瘤细胞和基质细胞。 TME 核心的肿瘤细胞协调复杂的信号，导致肿瘤生长、存活和对治疗的抵抗。人表皮生长因子受体 2 (HER2) 在相当大比例的浸润性乳腺癌中过度表达，影响预后和预测。通过利用抗体药物偶联物、单克隆抗体和酪氨酸激酶抑制剂等 HER2 靶向治疗，新的治疗方法针对 HER2 阳性乳腺癌。 HER2 阳性乳腺癌中的 TME 还涉及癌症相关成纤维细胞和癌症相关脂肪细胞，它们在肿瘤进展和治疗抵抗中发挥着关键作用。免疫微环境也发挥着重要作用，研究表明其对 HER2 阳性乳腺癌的预后有影响。曲妥珠单抗是首批针对 HER2 的单克隆抗体之一，已显示出有望提高 HER2 过表达乳腺癌的生存率。曲妥珠单抗与化疗的结合已证明早期乳腺癌治疗期间的无病生存率和总生存率显着提高。曲妥珠单抗通过抑制 HER2 信号通路发挥作用，导致细胞周期停滞并诱导细胞凋亡。总体而言，了解 HER2、肿瘤微环境和治疗干预之间复杂的相互作用对于改善 HER2 阳性 BC 的预后至关重要。

Breast cancer (BC) is the most common cancer and the second leading cause of cancer-related deaths in women globally. Despite advancements in treatment strategies, many patients still develop challenging-to-treat metastatic disease. The development and progression of tumors are influenced by genetic/epigenetic changes within tumor cells and alterations in the tumor microenvironment (TME) through a dynamic communication. The TME comprises various elements, including immune, tumor, and stromal cells. Tumor cells at the core of the TME orchestrate complex signals that lead to tumor growth, survival, and resistance to treatment. Human epidermal growth factor receptor 2 (HER2) is overexpressed in a significant proportion of invasive breast cancers, influencing prognosis and prediction. Novel therapeutic approaches target HER2-positive breast cancers by leveraging HER2-targeted therapeuirtcs such as antibody-drug conjugates, monoclonal antibodies, and tyrosine kinase inhibitors. The TME in HER2-positive breast cancers also involves cancer-associated fibroblasts and cancer-associated adipocytes, which play critical roles in tumor progression and therapy resistance. The immune microenvironment also plays a significant role, with studies indicating its impact on outcomes in HER2-positive breast cancer. Trastuzumab, one of the first monoclonal antibodies targeting HER2, has shown promise in enhancing survival rates in HER2-overexpressing breast cancer. Integration of trastuzumab with chemotherapy has demonstrated significant enhancements in disease-free survival as well as overall survival rates during early breast cancer treatment. Trastuzumab functions by inhibiting HER2 signaling pathways, leading to cell cycle arrest and induction of apoptosis. Overall, understanding the complex interplay between HER2, the tumor microenvironment, and therapeutic interventions is essential for improving outcomes in HER2-positive BC.