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However, the variability in treatment outcomes, such as pathological complete response (pCR) or relapse rates, underscores the need to identify predictive factors to optimize therapeutic strategies. This study aims to explore the relationship between clinicopathological factors and both pCR and disease-free survival (DFS) in an international cohort of patients with HER2+ BC, contributing to defining personalized treatment strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An international, multicenter, retrospective cohort study was conducted, including 517 patients with HER2+ BC who received neoadjuvant therapy comprising trastuzumab, pertuzumab, and chemotherapy. Data were collected between January 2016 and December 2023. The relationship between clinicopathological factors and treatment outcomes was analyzed using univariate tests, logistic regression for pCR, and Cox proportional hazards regression for DFS. Kaplan\u2013Meier survival curves with log-rank tests and hazard ratios were used to compare DFS across subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Multivariable analysis revealed that hormonal receptor (HR) expression and nodal status significantly predicted the achievement of pCR in this cohort. Factors such as age, HR status, tumor grade, Ki-67 index, nodal status, and pathological response were associated with relapse risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our real-world data demonstrates that a comprehensive approach considering pCR, age, HR status, and nodal involvement is essential for personalized treatment strategies. These factors should be taken into account when deciding whether to escalate or de-escalate treatment, contributing to improved HER2+ BC patient outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s12094-025-03937-7","type":"journal-article","created":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T13:24:30Z","timestamp":1746883470000},"page":"4160-4169","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Predictive factors for pCR and relapse following neoadjuvant dual HER2-blockade in HER2+ breast cancer: an international cohort study"],"prefix":"10.1007","volume":"27","author":[{"given":"Paulo","family":"Luz","sequence":"first","affiliation":[]},{"given":"Raquel","family":"Lopes-Br\u00e1s","sequence":"additional","affiliation":[]},{"given":"In\u00eas Soares","family":"de Pinho","sequence":"additional","affiliation":[]},{"given":"Vanessa","family":"Patel","sequence":"additional","affiliation":[]},{"given":"Miguel","family":"Esperan\u00e7a-Martins","sequence":"additional","affiliation":[]},{"given":"Lisa","family":"Gon\u00e7alves","sequence":"additional","affiliation":[]},{"given":"Joana","family":"Gon\u00e7alves","sequence":"additional","affiliation":[]},{"given":"Rita","family":"Freitas","sequence":"additional","affiliation":[]},{"given":"Diana","family":"Sim\u00e3o","sequence":"additional","affiliation":[]},{"given":"Maria Rold\u00e1n","family":"Galnares","sequence":"additional","affiliation":[]},{"given":"Silvia Artacho","family":"Criado","sequence":"additional","affiliation":[]},{"given":"Amanda","family":"Nobre","sequence":"additional","affiliation":[]},{"given":"Elias A. 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Lus\u00f3fona (Ref. CE.ECTS\/P23-23) after prior approval by the Ethics Committees of each hospital involved in this study to ensure compliance with national and international guidelines for research involving human subjects.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"This study and collection data were approved by the Ethics Committees of all hospitals involved, followed by the approval by the Ethics Committee of the School of Health Sciences and Technologies (Ref. CE.ECTS\/P23-23;\n                      \n                      ).Due to the retrospective and non-interventional nature of the study, no additional consents were required beyond the standard procedures for handling clinical data already established in each hospital.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}