{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T01:52:48Z","timestamp":1768269168237,"version":"3.49.0"},"reference-count":57,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,24]],"date-time":"2022-07-24T00:00:00Z","timestamp":1658620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Oncomine Clinical Research Grant Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Breast cancer during pregnancy (PrBC) is a rare tumor with only a little information on its immune landscape. Here, we sought to characterize the cellular composition of the tumor microenvironment (TME) of PrBC and identify its differences from early-onset breast cancer (EOBC) in non-pregnant women. A total of 83 PrBC and 89 EOBC were selected from our Institutional registry and subjected to tumor-infiltrating lymphocytes (TILs) profiling and immunohistochemistry for CD4, CD8, forkhead box P3 (FOXP3), and programmed death-ligand 1 (PD-L1) (clone 22C3). A significantly lower frequency of hormone receptor (HR)-positive tumors was observed in PrBC. The prevalence of low\/null PD-L1 and CD8+TILs was higher in PrBC than in the controls, specifically in HR+\/HER2\u2013 breast cancers. PrBC had a significantly higher risk of relapse and disease-related death, compared to EOBC. The presence of TILs and each TIL subpopulation were significantly associated with disease relapse. Moreover, the death rate was higher in PrBC with CD8+ TILs. The TME of PrBC is characterized by specific patterns of TIL subpopulations with significant biological and prognostic roles. Routine assessment of TILs and TILs subtyping in these patients would be a valid addition to the pathology report that might help identify clinically relevant subsets of women with PrBC.<\/jats:p>","DOI":"10.3390\/cells11152286","type":"journal-article","created":{"date-parts":[[2022,7,24]],"date-time":"2022-07-24T22:49:02Z","timestamp":1658702942000},"page":"2286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Breast Cancer during Pregnancy as a Special Type of Early-Onset Breast Cancer: Analysis of the Tumor Immune Microenvironment and Risk Profiles"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7401-1843","authenticated-orcid":false,"given":"Elham","family":"Sajjadi","sequence":"first","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy"},{"name":"Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0163-879X","authenticated-orcid":false,"given":"Konstantinos","family":"Venetis","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy"},{"name":"Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7115-139X","authenticated-orcid":false,"given":"Marianna","family":"Noale","sequence":"additional","affiliation":[{"name":"National Research Council (CNR), Neuroscience Institute Aging Branch, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Hatem A.","family":"Azim","sequence":"additional","affiliation":[{"name":"Breast Cancer Center, Hospital Zambrano Hellion, Tecnologico de Monterrey, San Pedro Garza Garcia 66278, NL, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Concetta","family":"Blundo","sequence":"additional","affiliation":[{"name":"Breast Surgery Unit, Fondazione IRCCS Ca\u2019 Granda\u2014Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppina","family":"Bonizzi","sequence":"additional","affiliation":[{"name":"Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenia","family":"Di Loreto","sequence":"additional","affiliation":[{"name":"Gynecology Unit, Fondazione IRCCS Ca\u2019 Granda\u2014Ospedale Maggiore Policlinico, 20122 Milan, 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Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Barberis","sequence":"additional","affiliation":[{"name":"Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Veronesi","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy"},{"name":"Division of Breast Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviana E.","family":"Galimberti","sequence":"additional","affiliation":[{"name":"Division of Breast Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Viale","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy"},{"name":"Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9101-9131","authenticated-orcid":false,"given":"Nicola","family":"Fusco","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy"},{"name":"Division of Pathology, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8227-8740","authenticated-orcid":false,"given":"Fedro A.","family":"Peccatori","sequence":"additional","affiliation":[{"name":"Fertility and Procreation Unit, Division of Gynecologic Oncology, IEO European Institute of Oncology 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