Macrophage polarization is associated with postoperative seroma development in breast cancer in the SerMa pilot cohort

Seroma formation is a frequent complication following mastectomy in the surgical treatment of breast cancer with profound consequences for the patients including possibly quality of life impairing implant complications. The pathogenesis remains unknown, leading to a lack of efficient preventive and curative strategies. The study's objective was to determine whether the macrophage infiltration of the tumor microenvironment and surrounding adipose tissue at the time of primary surgery is associated with postoperative seroma development. The observational monocentric SerMa pilot study was conducted from 12/2019 to 12/2022. We included 91 breast cancer and 9 carcinoma in situ cases treated with mastectomy at the University Hospital Augsburg, Germany. Patients with previous malignancies, metastatic disease and known immunodeficiency were excluded. The patients underwent different mastectomy procedures with or without implant- or expander-based breast reconstruction. The study's main outcome was seroma formation up to six months post-surgery, determined by clinical examination and fine needle aspiration of the seroma fluid if clinically necessary. Macrophage markers (CD68 and CD163) were immunohistochemically determined in formalin fixed paraffin-embedded slides containing the primary tumor and surrounding adipose tissue. Two groups were then formed as independent variables: cases with (seroma +) and without postoperative seroma formation (seroma-). Since all parameters in this study were not normally distributed, the non-parametric Mann-Whitney-U-test was used. A p-value < 0.05 was considered statistically significant. CD68 + cells (cases with seroma (seroma +): median = 90.7 cells, IQR = 62.5-130.5; cases without seroma (seroma-): median = 64.3 cells, IQR = 47.0-115-0, p = 0.036) and CD163 + cells (seroma + : median = 58.3 cells, IQR = 33.0-91.4; seroma-: median = 40.7 cells, IQR = 28.3-55.3, p = 0.027) in the tumor microenvironment and in the surrounding adipose tissue (CD68 + cells (seroma + : median = 8.0 cells, IQR = 5.3-11.0; seroma-: median = 4.7 cells, IQR = 3.0-10.0, p = 0.013), CD163 + cells (seroma + : median = 11.0 cells, IQR = 6.7-15.0; seroma-: median = 6.7 cells, IQR = 3.0-9.7, p = 0.016)) were significantly higher in cases with postoperative seroma formation compared to cases without. In the SerMa pilot study macrophage polarization within the primary tumor and surrounding adipose tissue was associated with post-operative seroma formation in breast cancer patients. This might be a suitable biomarker for predicting a higher risk of seroma formation.