High Numbers of CD163+ Tumor-Associated Macrophages Predict Poor Prognosis in HER2+ Breast Cancer

• Published in: Cancers Vol. 16; no. 3; p. 634
• Main Authors: Jääskeläinen, Minna M, Tumelius, Ritva, Hämäläinen, Kirsi, Rilla, Kirsi, Oikari, Sanna, Rönkä, Aino, Selander, Tuomas, Mannermaa, Arto, Tiainen, Satu, Auvinen, Päivi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2024
• Subjects: Breast cancer; Cancer therapies; CD163 antigen; Chemotherapy; Development and progression; Drug therapy; ErbB-2 protein; Health aspects; Macrophages; Medical prognosis; Medical research; Metastases; Metastasis; Patients; Pertuzumab; Prognosis; Radiation therapy; Statistics; Trastuzumab; Tumors; Finland; trastuzumab; breast cancer; tumor-associated macrophage; CD163; CD68; HER2
• ISSN: 2072-6694; 2072-6694
• 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.