曲妥珠单抗对乳腺癌巨噬细胞相关信号因子及预后的影响

doi:10.3969/j.issn.1006-6233.2024.11.08

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摘要 目的:探讨曲妥珠单抗对人类表皮生长因子受体2(HER2)阳性乳腺癌巨噬细胞相关信号因子及预后的影响。方法:选择2013年1月至2020年12月间在本院接受手术治疗的155名原发性非转移性HER2⁺乳腺癌患者。通过免疫组织化学染色分析肿瘤组织中CD8⁺、CD4⁺、FOXP3⁺肿瘤浸润淋巴细胞(TIL)和CD68⁺、CD163⁺ 肿瘤相关巨噬细胞(TAM)的水平。通过Spearman相关分析评估TIL和TAM之间的相关性。采用单变量和多变量Cox回归分析评估接受曲妥珠单抗辅助治疗患者的预后因素。结果:有32名(20.6%)患者在随访期间报告死亡。所有患者的中位随访时间为53.57个月(33.30~72.37)。FOXP3⁺ TIL计数与CD4⁺ TIL计数、CD8⁺ TIL计数呈正相关(P<0.001)。CD4⁺ TIL计数、CD8⁺ TIL计数、FOXP3⁺ TIL计数分别与CD163⁺ TAM、CD68⁺ TAM计数呈正相关(P<0.001)。Cox回归分析结果显示,淋巴血管侵犯(OR=2.631,95%CI=1.218~5.685),CD68⁺ TAM(OR=1.002,95%CI=1.001~1.003)、CD8⁺ TIL(OR=1.002,95%CI=1.001~1.004)、Ki-67增殖指数(OR=0.998,95%CI=0.997~1.000)是接受曲妥珠单抗辅助治疗患者预后的独立影响因素(P<0.05)。ROC分析显示,当CD68⁺ TAM的截止值为235.33时,其预测患者死亡的AUC为0.933(95%CI=0.896~0.970),敏感度为93.8%,特异度为83.7%。CD8⁺ TIL的截止值为53.67时,其预测患者死亡的AUC为0.645(95%CI=0.536~0.754),敏感度为56.3%,特异度为65.0%。结论:高CD68+ TAM计数、CD8⁺ TIL计数与接受曲妥珠单抗治疗的HER2⁺乳腺癌患者的不良预后相关,并且CD68⁺ TAM计数在预测不良预后方面具有较高的预测价值。

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	刘芳丽
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关键词 ：曲妥珠单抗, 乳腺癌, 人类表皮生长因子受体2, 肿瘤浸润淋巴细胞, 肿瘤相关巨噬细胞

Abstract：Objective: To investigate the impact of trastuzumab on macrophage-related signaling factors and prognosis in human epidermal growth factor receptor 2 (HER2)-positive breast cancer.Methods: A total of 155 patients with primary, non-metastatic HER2⁺ breast cancer who underwent surgery between January 2013 and December 2020 were enrolled in this study. Immunohistochemistry was used to analyze the expression levels of CD8⁺, CD4⁺, FOXP3⁺ tumor-infiltrating lymphocytes (TILs) and CD68⁺, CD163⁺ tumor-associated macrophages (TAMs) in tumor tissues. Spearman correlation analysis was used to assess the correlation between TILs and TAMs. Univariate and multivariate Cox regression analyses were performed to evaluate prognostic factors in patients who received adjuvant trastuzumab therapy.Results: Thirty-two patients (20.6%) died during the follow-up period. The median follow-up time for all patients was 53.57 months (range, 33.30~72.37). FOXP3⁺ TIL counts were positively correlated with CD4⁺ and CD8⁺ TIL counts (P<0.001). CD4⁺, CD8⁺, and FOXP3⁺ TIL counts were positively correlated with CD163⁺ and CD68⁺ TAM counts (P<0.001). Cox regression analysis showed that lymphovascular invasion (OR=2.631, 95% CI=1.218-5.685), CD68⁺ TAM (OR=1.002, 95% CI=1.001-1.003), CD8⁺ TIL (OR=1.002, 95% CI=1.001-1.004), and Ki-67 proliferation index (OR=0.998, 95% CI=0.997-1.000) were independent prognostic factors for patients receiving adjuvant trastuzumab therapy (P<0.05). ROC analysis showed that when the cutoff value for CD68⁺ TAM was 235.33, the AUC for predicting patient death was 0.933 (95% CI=0.896~0.970), with a sensitivity of 93.8% and a specificity of 83.7%. When the cutoff value for CD8⁺ TIL was 53.67, the AUC for predicting patient death was 0.645 (95% CI=0.536-0.754), with a sensitivity of 56.3% and a specificity of 65.0%.Conclusion: High counts of CD68⁺ TAM and CD8⁺ TIL were associated with poor prognosis in HER2⁺ breast cancer patients receiving trastuzumab therapy, and CD68⁺ TAM counts had a higher predictive value for adverse prognosis.

Key words： Trastuzumab Breast cancer Human epidermal growth factor receptor 2 Tumor-infiltrating lymphocytes Tumor-associated macrophages

基金资助:陕西省卫生健康委员会科研项目,(编号:2020131211)

通讯作者: 周晓燕

引用本文:

刘芳丽, 周晓燕. 曲妥珠单抗对乳腺癌巨噬细胞相关信号因子及预后的影响[J]. 河北医学, 2024, 30(11): 1803-1808.
LIU Fangli, ZHOU Xiaoyan. Impact of Trastuzumab on Macrophage-Related Signaling Factors and Prognosis in Breast Cancer. HeBei Med, 2024, 30(11): 1803-1808.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2024.11.08 或 http://www.hbyxzzs.cn/CN/Y2024/V30/I11/1803

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