{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T21:01:47Z","timestamp":1778360507567,"version":"3.51.4"},"reference-count":27,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDB\/00215\/2020"],"award-info":[{"award-number":["UIDB\/00215\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDP\/00215\/2020"],"award-info":[{"award-number":["UIDP\/00215\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["LA\/P\/0064\/2020"],"award-info":[{"award-number":["LA\/P\/0064\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Breast cancer is the most common malignant neoplasm in women and the leading cause of cancer-related death. Approximately 50% of HER2-negative breast cancers exhibit low expression of this protein (HER2-low). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate targeting the HER2 receptor which has shown benefit in patients with HER2-low metastatic breast cancer in the DESTINY-Breast04 study. However, few data are available on its efficacy in real-world practice. Methods: We conducted a retrospective multicenter national study (eight centers) including patients with advanced HER2-low breast cancer (immunohistochemistry 1+ or 2+\/ in situ hybridization negative) who started T-DXd treatment between January 2022 and March 2024. Patients had received at least one previous line of treatment. The primary endpoint was real-world progression-free survival (rwPFS) in patients with metastatic HER2-low breast cancer treated with T-DXd. The secondary endpoints were real-world overall survival (OS) and objective response rate (ORR). Results: The study included 35 patients (34 female and 1 male patient), with a median age of 54 years at the start of T-DXd. All patients had an ECOG-PS 0\u20131, and 26 patients (74%) had hormone receptor (HR)-positive disease. The median number of prior lines of treatment was 4 [1\u20137], and 23 patients (65.8%) had metastases in three or more sites. With a median follow-up of 7.8 months, rwPFS was 6 months (95% CI, 2.3\u20139.7), and OS was 15 months (95% CI, 4.7\u201325.3). In HR-positive patients, the median rwPFS was 6 months (95% CI, 1.2\u201310.7), compared to 4 months (95% CI, 2.1\u20135.9) in HR-negative patients. The overall ORR was 52.9%. Adverse events of grade 3 or higher were neutropenia (2.9%) and fatigue (2.9%). Conclusions: This study provides real-world data on T-DXd in the treatment of advanced HER2-low breast cancer. It is noteworthy that the population was heavily pre-treated and had a higher proportion of HR-negative patients, which may explain the lower efficacy compared to the DESTINY-Breast04 study.<\/jats:p>","DOI":"10.3390\/cancers17121911","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T04:23:02Z","timestamp":1749442982000},"page":"1911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Trastuzumab Deruxtecan in Previously Treated HER2-Low Metastatic Breast Cancer: Real-World Multicentric Study in the Portuguese Population"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5929-4731","authenticated-orcid":false,"given":"Lu\u00edsa","family":"Soares Miranda","sequence":"first","affiliation":[{"name":"Servi\u00e7o de Oncologia M\u00e9dica, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, 4099-001 Porto, Portugal"},{"name":"Oncology Research UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laborat\u00f3rio para a Investiga\u00e7\u00e3o Integrativa e Translacional em Sa\u00fade Populacional (ITR), University of Porto, 4050-600 Porto, Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Sousa","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oncologia M\u00e9dica, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, 4099-001 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7488-7340","authenticated-orcid":false,"given":"Miguel","family":"Martins Braga","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oncologia M\u00e9dica, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, 4099-001 Porto, Portugal"}]},{"given":"Marisa","family":"Couto","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oncologia M\u00e9dica, Unidade Local de Sa\u00fado de S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"given":"Isabel","family":"Vieira Fernandes","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oncologia M\u00e9dica, Instituto Portugu\u00eas de Oncologia de Coimbra Francisco Gentil, 3000-075 Coimbra, Portugal"}]},{"given":"Francisca","family":"Abreu","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oncologia M\u00e9dica, Hospital Senhora de Oliveira, Unidade Local de Sa\u00fade Alto Ave, 4835-044 Guimaraes, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1760-3436","authenticated-orcid":false,"given":"In\u00eas","family":"Eiriz","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oncologia M\u00e9dica, Hospital Prof. Dr. Fernando Fonseca, Unidade Local de Sa\u00fade Amadora-Sintra, 2720-276 Amadora, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5619-5463","authenticated-orcid":false,"given":"Catarina","family":"Lopes Fernandes","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oncologia M\u00e9dica, Hospital Pedro Hispano, Unidade Local de Sa\u00fade de Matosinhos, 4464-513 Matosinhos, Portugal"}]},{"given":"Alice","family":"Fonseca Marques","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oncologia M\u00e9dica, Unidade Local de Sa\u00fade de Coimbra, 3004-561 Coimbra, Portugal"}]},{"given":"Maria Teresa","family":"Marques","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oncologia M\u00e9dica, Hospital de S\u00e3o Bernardo, Unidade Local de Sa\u00fade da Arr\u00e1bida, 2910-446 Set\u00fabal, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-7387","authenticated-orcid":false,"given":"Raquel","family":"Rom\u00e3o","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oncologia M\u00e9dica, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, 4099-001 Porto, Portugal"}]},{"given":"Fernando","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oncologia M\u00e9dica, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, 4099-001 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3587-8214","authenticated-orcid":false,"given":"Joana","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oncologia M\u00e9dica, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, 4099-001 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7267-3584","authenticated-orcid":false,"given":"Ant\u00f3nio","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Oncologia M\u00e9dica, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, 4099-001 Porto, Portugal"},{"name":"Oncology Research UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS-School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"Laborat\u00f3rio para a Investiga\u00e7\u00e3o Integrativa e Translacional em Sa\u00fade Populacional (ITR), University of Porto, 4050-600 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/ijc.35278","article-title":"The GLOBOCAN 2022 cancer estimates: Data sources, methods, and a snapshot of the cancer burden worldwide","volume":"156","author":"Filho","year":"2024","journal-title":"Int. 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