{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:10:40Z","timestamp":1773033040582,"version":"3.50.1"},"reference-count":113,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T00:00:00Z","timestamp":1636848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Breast Cancer (BC) is the second most frequent cause of cancer death among women worldwide and, although there have been significant advances in BC therapies, a significant percentage of patients develop metastasis and disease recurrence. Since BC was demonstrated to be an immunogenic tumor, immunotherapy has broken through as a significant therapy strategy against BC. Over the years, immunotherapy has improved the survival rate of HER2+ BC patients due to the approval of some monoclonal antibodies (mAbs) such as Trastuzumab, Pertuzumab and, recently, Margetuximab, along with the antibody-drug conjugates (ADC) Trastuzumab-Emtansine (T-DM1) and Trastuzumab Deruxtecan. Immune checkpoint inhibitors (ICI) showed promising efficacy in triple-negative breast cancer (TNBC) treatment, namely Atezolizumab and Pembrolizumab. Despite the success of immunotherapy, some patients do not respond to immunotherapy or those who respond to the treatment relapse or progress. The main causes of these adverse events are the complex, intrinsic or extrinsic resistance mechanisms. In this review, we address the different immunotherapy approaches approved for BC and some of the mechanisms responsible for resistance to immunotherapy.<\/jats:p>","DOI":"10.3390\/biomedicines9111687","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T20:51:53Z","timestamp":1636923113000},"page":"1687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Immunotherapy in Breast Cancer: When, How, and What Challenges?"],"prefix":"10.3390","volume":"9","author":[{"given":"Beatriz","family":"Henriques","sequence":"first","affiliation":[{"name":"Polit\u00e9cnico de Coimbra, ESTeSC, UCPCBL, 3046-854 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5205-8939","authenticated-orcid":false,"given":"Fernando","family":"Mendes","sequence":"additional","affiliation":[{"name":"Polit\u00e9cnico de Coimbra, ESTeSC, UCPCBL, 3046-854 Coimbra, Portugal"},{"name":"Laborat\u00f3rio de Investiga\u00e7\u00e3o em Ci\u00eancias Aplicadas \u00e0 Sa\u00fade (LabinSa\u00fade), Polit\u00e9cnico de Coimbra, ESTESC, 3046-854 Coimbra, Portugal"},{"name":"Biophysics Institute of Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal"},{"name":"European Association for Professions in Biomedical Sciences, B-1000 Brussels, Belgium"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1457-8992","authenticated-orcid":false,"given":"Diana","family":"Martins","sequence":"additional","affiliation":[{"name":"Polit\u00e9cnico de Coimbra, ESTeSC, UCPCBL, 3046-854 Coimbra, Portugal"},{"name":"Laborat\u00f3rio de Investiga\u00e7\u00e3o em Ci\u00eancias Aplicadas \u00e0 Sa\u00fade (LabinSa\u00fade), Polit\u00e9cnico de Coimbra, ESTESC, 3046-854 Coimbra, Portugal"},{"name":"Biophysics Institute of Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment Genetics and Oncobiology (CIMAGO), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-504 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sivaganesh, V., Promi, N., Maher, S., and Peethambaran, B. 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