Tumor-associated macrophages (TAMs) are associated with a poor outcome in breast cancer (BC), but their prognostic value in different BC subtypes has remained somewhat unclear. Here, we investigated the prognostic value of M2-like TAMs (CD163+) and all TAMs (CD68+) in a patient cohort of 278 non-metastatic BC patients, half of whom were HER2+ (n= 139). The survival endpoints investigated were overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS). In the whole patient cohort (n= 278), a high CD163+ TAM count and a high CD68+ TAM count were associated with a worse outcome (p≤ 0.023). In HER2+ BC, a high CD163+ TAM count was an independent factor for a poor prognosis across all the investigated survival endpoints (p< 0.001). The prognostic effect was evident in both the HER2+/hormone receptor-positive (p< 0.001) and HER2+/hormone receptor-negative (p≤ 0.012) subgroups and regardless of the provision of adjuvant trastuzumab (p≤ 0.002). In HER2-negative BC, the CD163+ TAM count was not significantly associated with survival. These results suggest that a high CD163+ TAM count predicts an inferior outcome, especially in HER2+ BC patients, and as adjuvant trastuzumab did not overcome the poor prognostic effect, combination treatments including therapies targeting the macrophage function could represent an effective therapeutic approach in HER2+ BC.
肿瘤相关巨噬细胞（TAMs）与乳腺癌不良预后相关，但其在不同乳腺癌亚型中的预后价值尚不完全明确。本研究在278例非转移性乳腺癌患者队列中评估了M2型TAMs（CD163+）和总TAMs（CD68+）的预后价值，其中半数患者为HER2阳性（n=139）。研究的生存终点包括总生存期（OS）、乳腺癌特异性生存期（BCSS）和无病生存期（DFS）。在整个患者队列（n=278）中，高CD163+ TAM计数和高CD68+ TAM计数均与不良预后相关（p≤0.023）。在HER2阳性乳腺癌中，高CD163+ TAM计数是所有研究生存终点的独立不良预后因素（p<0.001）。这种预后效应在HER2+/激素受体阳性（p<0.001）和HER2+/激素受体阴性（p≤0.012）亚组中均显著存在，且不受辅助曲妥珠单抗治疗的影响（p≤0.002）。在HER2阴性乳腺癌中，CD163+ TAM计数与生存率无显著相关性。这些结果表明，高CD163+ TAM计数可预测不良预后，尤其在HER2阳性乳腺癌患者中。由于辅助曲妥珠单抗未能克服其不良预后效应，针对巨噬细胞功能的联合治疗方案可能成为HER2阳性乳腺癌的有效治疗策略。
High Numbers of CD163+ Tumor-Associated Macrophages Predict Poor Prognosis in HER2+ Breast Cancer
肿瘤(癌症)患者之家