乳腺癌新辅助化疗联合靶向治疗皮下与静脉制剂对比

Comparison of Subcutaneous and Intravenous Formulations in Neoadjuvant Chemotherapy Combined with Targeted Therapy for Breast Cancer

摘要: 人表皮生长因子受体2 (HER2)阳性乳腺癌是乳腺癌领域极具代表性的亚型，约占全部乳腺癌病例的20%~30%，该亚型肿瘤恶性程度高、侵袭性强、疾病进展快、早期易发生淋巴结转移，复发率及病死率高，患者总体预后较差，是临床治疗的重点与难点。新辅助化疗联合抗HER2靶向治疗已成为HER2阳性局部晚期乳腺癌的标准初始治疗方案，可有效实现肿瘤降期、提高根治性手术切除率与保乳率，同时能评估体内肿瘤对治疗方案的敏感性，为后续全程治疗策略制定提供关键依据。传统抗HER2靶向药物以静脉输注制剂为临床主流剂型，虽疗效确切，但存在给药流程繁琐、静脉血管损伤、输注不良反应、患者就诊耗时久等诸多短板，影响治疗依从性与整体生活质量。随着生物制药技术的不断升级，曲妥珠单抗单药皮下制剂、曲妥珠单抗联合帕妥珠单抗固定剂量复方皮下制剂相继获批应用于乳腺癌新辅助、辅助治疗，依托透明质酸酶的促吸收作用，实现了固定剂量、快速给药的治疗新模式，打破了静脉制剂的临床局限。本文旨在系统对比皮下与静脉制剂在HER2阳性乳腺癌新辅助治疗中的疗效、安全性、经济性、依从性及特殊人群应用差异，为临床个体化选择提供循证依据。

Abstract: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a highly representative subtype of breast cancer, accounting for approximately 20%~30% of all breast cancer cases. This subtype is characterized by high tumor malignancy, strong invasiveness, rapid disease progression, frequent early lymph node metastasis, high recurrence and mortality rates, and poor overall patient prognosis, making it a key and challenging focus of clinical treatment. Neoadjuvant chemotherapy combined with anti-HER2 targeted therapy has become the standard initial treatment regimen for HER2-positive locally advanced breast cancer. It can effectively achieve tumor downstaging, improve the rates of radical surgical resection and breast conservation, evaluate the in vivo tumor sensitivity to treatment regimens, and provide critical evidence for the formulation of subsequent whole-course treatment strategies. Traditional anti-HER2 targeted drugs are predominantly administered via intravenous infusion in clinical practice. Despite their definite efficacy, they have multiple limitations including cumbersome administration procedures, intravenous vascular damage, infusion-related adverse reactions, and long hospital visiting time for patients, which impair treatment adherence and overall quality of life. With the continuous upgrading of biopharmaceutical technologies, single-agent subcutaneous trastuzumab and fixed-dose combination subcutaneous formulation of trastuzumab plus pertuzumab have been successively approved for neoadjuvant and adjuvant therapy of breast cancer. Relying on the absorption-promoting effect of hyaluronidase, these formulations have established a new treatment mode with fixed dose and rapid administration, breaking the clinical limitations of intravenous preparations. This paper systematically compares the differences in efficacy, safety, economy, treatment adherence, and application in special populations between subcutaneous and intravenous formulations in the neoadjuvant therapy of HER2-positive breast cancer, so as to provide evidence-based references for clinical individualized treatment selection.