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Accelerated Partial Breast Irradiation: Macrophage Polarisation Shift Classification Identifies High-Risk Tumours in Early Hormone Receptor-Positive Breast Cancer

1
Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, D-91054 Erlangen, Germany
2
Institute of Pathology, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstraße 8-10, D-91054 Erlangen, Germany
3
Department of Nephropathology, Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstraße 8-10, D-91054 Erlangen, Germany
4
Department of Gynecology and Obstetrics, Universitätsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 21, D-91054 Erlangen, Germany
5
Intensive Care Unit, Redcliffe Hospital; University of Queensland, 4072 Brisbane, Queensland, Australia
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(2), 446; https://doi.org/10.3390/cancers12020446
Received: 14 January 2020 / Revised: 7 February 2020 / Accepted: 9 February 2020 / Published: 14 February 2020
Studies have demonstrated correlations between accumulations of tumour-associated macrophages (TAMs), especially of M2-like phenotype, and increased mortality in advanced breast cancer. We investigated the prognostic potential of both main macrophage phenotypes in early hormone receptor-positive (HR+) breast cancer. The studied cohort of 136 patients participated in an institutional APBI phase II trial. Patient selection was characterized by HR+, small tumour size and no metastasis. Tissue microarrays from pre-RT resection samples were double stained for CD68/CD163 using immunohistochemistry. CD68+/CD163− cells were considered M1-like macrophages and CD68+/CD163+ was representative of M2-like macrophages. M1 and M2 macrophage densities were analysed semi-automatically in the stromal and intraepithelial tumour compartment. Low M1 and high M2 densities were strongly associated with decreased disease-free survival (DFS). Combined TAM phenotype densities were studied after defining a macrophage shift classification: M1-shifted (M1 high, M2 low) and non-shifted (M1 low, M2 low; M1 high, M2 high) tumours entailed a favourable outcome. In contrast, M2-shifted (M1 low, M2 high) TAM populations were associated with extremely reduced DFS. Thus, the full predictive potential of TAMs was revealed in a combined analysis of both phenotypes. The M2-shifted subgroup of tumours is classified as high-risk and probably not suitable for partial breast irradiation. View Full-Text
Keywords: tumour associated macrophages; CD68; CD163; prognosis; early breast cancer; hormone receptor-positive; accelerated partial breast irradiation tumour associated macrophages; CD68; CD163; prognosis; early breast cancer; hormone receptor-positive; accelerated partial breast irradiation
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Schnellhardt, S.; Erber, R.; Büttner-Herold, M.; Rosahl, M.-C.; Ott, O.J.; Strnad, V.; Beckmann, M.W.; King, L.; Hartmann, A.; Fietkau, R.; Distel, L. Accelerated Partial Breast Irradiation: Macrophage Polarisation Shift Classification Identifies High-Risk Tumours in Early Hormone Receptor-Positive Breast Cancer. Cancers 2020, 12, 446.

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