Department of Pharmacology, College of Medicine, University of Basrah, Basrah, Iraq.
Department of Medicine, College of Medicine, University of Basrah, Basrah, Iraq.
J Med Life. 2023 Nov;16(11):1633-1638. doi: 10.25122/jml-2023-0163.
HER-2-positive breast cancer is characterized by its aggressive nature, poor prognosis, and reduced overall survival. The emergence of trastuzumab resistance is currently considered a global problem. The immune system plays a pivotal role in tumor progression and development. Cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and other immune checkpoint proteins may be potential prognostic factors and therapeutic targets for breast cancer. This study aimed to determine the correlation between CTLA-4 expression in peripheral blood and insulin-like growth factor-1 (IGF-1) serum levels and their impact on trastuzumab responsiveness in HER-2-positive patients with breast cancer. CTLA-4 expression was analyzed in peripheral blood cells using quantitative PCR, while IGF-1 serum levels were assessed through electrochemiluminescence assays. There was a significant increase in CTLA-4 expression at cycle 9, which continued to increase until it reached 4.6 at cycle 17. High IGF-1 levels were observed in newly diagnosed HER-2 positive patients before trastuzumab therapy, significantly decreasing post-therapy (p=0.001). Co-targeting HER-2 and IGF-1 receptors may reduce the risk of recurrence and improve outcomes. In addition, targeted CTLA-4 molecules may improve patient survival and prevent recurrence.
人表皮生长因子受体 2 阳性乳腺癌的特点是侵袭性强、预后差、总生存期缩短。曲妥珠单抗耐药的出现目前被认为是一个全球性问题。免疫系统在肿瘤的发生和发展中起着关键作用。细胞毒性 T 淋巴细胞相关蛋白 4（CTLA-4）和其他免疫检查点蛋白可能是乳腺癌的潜在预后因素和治疗靶点。本研究旨在确定人表皮生长因子受体 2 阳性乳腺癌患者外周血 CTLA-4 表达与胰岛素样生长因子 1（IGF-1）血清水平的相关性及其对曲妥珠单抗反应性的影响。采用实时定量 PCR 分析外周血细胞中 CTLA-4 的表达，采用电化学发光法检测 IGF-1 血清水平。在第 9 个周期时 CTLA-4 表达显著增加，持续增加至第 17 个周期时达到 4.6。在曲妥珠单抗治疗前，新诊断的人表皮生长因子受体 2 阳性患者的 IGF-1 水平较高，治疗后显著下降（p=0.001）。联合靶向 HER-2 和 IGF-1 受体可能降低复发风险并改善结局。此外，靶向 CTLA-4 分子可能改善患者的生存并预防复发。
