{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:19:29Z","timestamp":1792588769931,"version":"4.5.0"},"reference-count":34,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,15]],"date-time":"2024-09-15T00:00:00Z","timestamp":1726358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Tumor-associated neutrophils (TANs) are important modulators of the tumor microenvironment with opposing functions that can promote and inhibit tumor progression. The prognostic role of TANs in early luminal breast cancer is unclear. Methods: A total of 144 patients were treated for early-stage hormone-receptor-positive breast cancer as part of an Accelerated Partial Breast Irradiation (APBI) phase II trial. Resection samples from multiple locations were processed into tissue microarrays and sections thereof immunohistochemically stained for CD66b+ neutrophils. CD66b+ neutrophil density was measured separately in the stromal and intraepithelial compartment. Results: High stromal and intraepithelial CD66b+ TAN density was a negative prognostic factor in central tumor samples. In addition, neutrophil density in adjacent normal breast tissue and lymph node samples also correlated with reduced disease-free survival. TAN density correlated with CD163+ M2-like tumor-associated macrophage (TAM) density, which we analyzed in a previous study. TANs were a negative prognostic factor in tumors with an elevated M1\/M2 TAM ratio, while this impact on patient outcome was lost in tumors with a low M1\/M2 ratio. A combined multivariate analysis of TAM and TAN density revealed that only TAM polarization status was an independent prognostic factor. Conclusions: CD66b+ neutrophils were a negative prognostic factor in early-stage luminal breast cancer in single-marker analysis. Combined analysis with TAMs could be necessary to correctly evaluate their prognostic impact in future studies. TAN recruitment might act as a compensatory mechanism of immunoevasion and disease progression in tumors that are unable to sufficiently attract and polarize TAMs.<\/jats:p>","DOI":"10.3390\/cancers16183160","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T10:56:57Z","timestamp":1726484217000},"page":"3160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Tumor-Associated Neutrophils Are a Negative Prognostic Factor in Early Luminal Breast Cancers Lacking Immunosuppressive Macrophage Recruitment"],"prefix":"10.3390","volume":"16","author":[{"given":"Eva","family":"Schmidt","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8040-3226","authenticated-orcid":false,"given":"Luitpold","family":"Distel","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0315-1229","authenticated-orcid":false,"given":"Ramona","family":"Erber","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Universit\u00e4tsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9974-6683","authenticated-orcid":false,"given":"Maike","family":"B\u00fcttner-Herold","sequence":"additional","affiliation":[{"name":"Department of Nephropathology, Institute of Pathology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Charlotte","family":"Rosahl","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5806-6158","authenticated-orcid":false,"given":"Oliver J.","family":"Ott","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vratislav","family":"Strnad","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin C.","family":"Hack","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Universit\u00e4tsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Universit\u00e4tsklinikum Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hecht","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy and Radiation Oncology, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Fietkau","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0418-4401","authenticated-orcid":false,"given":"S\u00f6ren","family":"Schnellhardt","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy and Radiation Oncology, Saarland University Medical Center, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1097\/GRF.0000000000000239","article-title":"Breast Cancer Epidemiology and Risk Factors","volume":"59","author":"Rojas","year":"2016","journal-title":"Clin. 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