Jääskeläinen Minna M, Tumelius Ritva, Hämäläinen Kirsi, Rilla Kirsi, Oikari Sanna, Rönkä Aino, Selander Tuomas, Mannermaa Arto, Tiainen Satu, Auvinen Päivi
Cancer Center, Kuopio University Hospital, Wellbeing Services County of North Savo, 70029 Kuopio, Finland.
Institute of Clinical Medicine, University of Eastern Finland, 70211 Kuopio, Finland.
Cancers (Basel). 2024 Feb 1;16(3):634. doi: 10.3390/cancers16030634.
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+ ( = 139). The survival endpoints investigated were overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS). In the whole patient cohort ( = 278), a high CD163+ TAM count and a high CD68+ TAM count were associated with a worse outcome ( ≤ 0.023). In HER2+ BC, a high CD163+ TAM count was an independent factor for a poor prognosis across all the investigated survival endpoints ( < 0.001). The prognostic effect was evident in both the HER2+/hormone receptor-positive ( < 0.001) and HER2+/hormone receptor-negative ( ≤ 0.012) subgroups and regardless of the provision of adjuvant trastuzumab ( ≤ 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（TAM）与乳腺癌（BC）的不良预后相关，但其在不同BC亚型中的预后价值仍不太明确。在此，我们调查了278例非转移性BC患者队列中M2样TAM（CD163 +）和所有TAM（CD68 +）的预后价值，其中一半患者为HER2 +（n = 139）。所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计数与较差的预后相关（P≤0.023）。在HER2 + BC中，高CD163 + TAM计数是所有研究生存终点预后不良的独立因素（P<0.001）。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，以及无论是否提供辅助曲妥珠单抗（P≤0.002），预后效应均明显。在HER2阴性BC中，CD163 + TAM计数与生存无显著相关性。这些结果表明，高CD163 + TAM计数预示着较差的预后，尤其是在HER2 + BC患者中，并且由于辅助曲妥珠单抗未能克服不良预后效应，包括针对巨噬细胞功能的疗法在内的联合治疗可能是HER2 + BC的一种有效治疗方法。
