Abstract

Abstract Background The primary objective of the SerMa pilot study was to identify possible immunological or inflammatory factors related to seroma formation after mastectomy in cases with primary breast cancer. Preliminary data suggest a distinct association between age and seroma formation. The work presented here investigates therefore a possible link between age and differences in the microenvironment represented by tumor-associated macrophages. The latter have been characterized by the expression of CD68 and CD163 receptors, that are markers of cells from the monocyte/macrophage lineage with known clinical implications. Methods Tumor tissue of 80 primary breast cancer cases of the SerMa pilot study was available for further analyses. Immunohistochemistry based on antibody staining against CD68 and CD163 was used and due to the mean age of 63 years two groups were formed and compared: patients aged under 63 and patients aged 63 and older. The number of macrophages (standardized manually quantified) was compared in these two groups regarding seroma formation. Results Seroma formation occurred significantly more frequently with older age of the patient (p < 0.001). For the overall cohort, the number of CD68-positive macrophages was significantly increased (p=0.036) in patients with seroma formation, as well as for CD163 (p=0.027). The macrophage polarization was shown to be independent of tumor biological characteristics (p > 0.130). However, closer examination revealed an age-dependent effect of the macrophage polarization. In the group 63 years and older, there was no significant difference in the number of CD68- or CD163-positive macrophages (p = 0.610 and p = 0.425, respectively) in relation to seroma formation. A significant effect was seen in this analysis only in patients younger than 63 regarding CD163 (p < 0.001) and a non-significant trend for CD68 (p = 0.065). Conclusions These data demonstrate an age-dependent significant correlation of CD163 positive macrophages measured in the tumor environment with seroma formation in the breast after mastectomy. For CD68 positive macrophages a trend was seen, but didn’t reach statistical significance due to the small number of cases. These data show a different immunological response in tumor tissue depending on age and therefore support the thesis that seroma formation is primarily related to immunological/inflammatory processes. In the future, detection of CD163-positive macrophages in the tumor microenvironment could therefore be considered a marker for patients under 63 years at increased risk of seroma. The planned international SerMa study (EUBREAST 5) will have to show whether these results can be transferred to a prospective design with higher case number. Citation Format: Melitta Koepke, Felicitas Schneider, Christina Kuhn, Mathis Wild, Mariella Schneider, Nicole Pochert, Claudia Traidl-Hoffmann, Jacqueline Sagasser, Christian Dannecker, Christian Hinske, Maggie Banys-Paluchowski, Michael Untch, Thorsten Kühn, Udo Jeschke, Nina Ditsch. SerMa (Seroma of the Mammary gland) pilot - Is there a possible link between macrophage-based immune response and age? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-06.

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