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To explore relapse dynamics, multivariate Cox regression models and annual hazard rates of relapses were reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 1493 relapses, early, intermediate, and late relapses represented 28.3%, 29.7%, and 42.1% of all relapses, respectively. In 1050 patients, of both early and late relapses, age\u2009&gt;\u200970\u00a0years (odds ratio [OR] 5.13; 95% confidence interval [CI] 3.23\u20138.15), stage III (OR 3.22; 95% CI 1.90\u20135.46), histological grade 3 (OR, 2.93; 95% CI 1.69\u20135.10), and HR\u2009\u2212\u2009\/HER2\u2009\u2212\u2009subtype (OR 10.26; 95% CI 6.55\u201316.05) were associated with an increase of early relapse risk. Annual hazard rate of loco-regional relapses (LRR) steadily increased over time in patients with HR\u2009+\u2009\/HER2\u2009\u2212\u2009tumors, while those with HR\u2009\u2212\u2009\/HER2\u2009\u2212\u2009tumors exhibited a fluctuating pattern. For distant relapses (DR), the hazard rate peaked at 2\u00a0years and then rise steadily in HR\u2009+\u2009\/HER2\u2009\u2212\u2009tumors whereas remained variable in HR\u2009\u2212\u2009\/HER2\u2009\u2212\u2009tumors. In multivariate Cox model, LRR was associated with stage, subtype, and histological grade, while DR was additionally influenced by age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Age at diagnosis, stage, histological grade, and tumor subtype were associated with distinct relapse timing patterns. These findings support further research into relapse dynamics and predictors by analyzing real-world data.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12094-026-04419-0","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T16:52:13Z","timestamp":1783097533000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical and pathologic insights into early and late breast cancer relapses: a real-world analysis from the El \u00c1lamo IV registry"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8274-1811","authenticated-orcid":false,"given":"Luc\u00eda","family":"Fraile-Lara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Andr\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Servitja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Carrasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"Guerrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Bermejo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ant\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefina","family":"Cruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"\u00c1lvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Aguiar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purificaci\u00f3n","family":"Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Rodr\u00edguez-Lescure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Blasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"L\u00f3pez-Tarruella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"4419_CR1","unstructured":"Ferlay J, M E, Lam F, Laversanne M, Colombet M, Mery L, et al. 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Dr. Raquel Andr\u00e9s has received speaker honoraria by Daiichi Sankyo, Lilly, and Novartis and advisory by MSD\u00a0and AstraZeneca. Dr. Sonia Servitja has received speaker honoraria by Daiichi-Sankyo, AstraZeneca, Roche Pharma and Novartis and advisory by Seagen, Genomic Health, MSD, and Daiichi Sankyo. Eva Carrasco has stock and other ownership interests from Lilly, has received travel and accommodations support from Roche and her husband has participated in consulting and advisory board activities with Bristol-Myers Squibb, Novartis, Celgene, Roche Pharma, Janssen, Amgen, Incyte, Abbvie and Pfizer, has received travel and accommodations support from Celgene, Novartis, and Bristol-Myers Squibb. His institution has received research funding from Celgene, Janssen, Bristol-Myers Squibb, Novartis, Celgene, Roche\/Genentech, Amgen, Pfizer, and Abbvie. GEICAM has received research funding from Roche\/Genentech, Bristol-Myers Squibb, Novartis, Pfizer, Celgene, AstraZeneca, Merck Sharp & Dohme, Pierre Fabre, and Takeda. Dr. Angel Guerrero has received an institutional grant by Pfizer, advisory by Novartis, Palex, Pfizer, AstraZeneca, Pierre Fabre, travel grant by Roche Pharma, Pfizer and Novartis and speaker honoraria by Novartis, Pfizer, Lilly, Pfizer, AstraZeneca. Dr. Antonio Ant\u00f3n has received speaker honoraria by Astrazeneca-Daiichi-Sankyo, Eli Lilly and Seagen, advisory by AstraZeneca-Daichii-Sankyo, Eli Lilly, Gilead and personal grant by AstraZeneca-Daiichi Sankyo, Eli Lilly, Gilead, Pfizer and Seagen. Dr. Josefina Cruz has received honoraria by Astrazeneca, Roche Pharma, Novartis, PharmaMar, Pierre Fabre, Eisai, Lilly, Daiichi Sankyo, Seagen, Gilead and Pfizer and advisory by Astrazeneca, Roche Pharma, Novartis, PharmaMar, Eisai, Lilly, GlaxoSmithKline, Pfizer, Gilead, Seagen and Daiichi Sankyo. Dr. Isabel \u00c1lvarez has received speaker honoraria by Roche Pharma, advisory by AstraZeneca, Pfizer, Novartis, Roche Pharma and Gilead and research funding by AstraZeneca, Pfizer, Novartis and Roche Pharma. Dr. \u00c1lvaro Rodr\u00edguez-Lescure has received speaker honoraria by Pfizer, Novartis, AstraZeneca, Daichii-Sankyo and Seagen and advisory by Pfizer, Novartis, Roche, AstraZeneca, Daiichi Sankyo, Pierre Fabre and Seagen. Dr. Miguel Mart\u00edn has received consulting fees from AstraZeneca, Amgen, Taiho Oncology, Roche\/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, Taiho Oncology and Pfizer; speakers\u2019 honoraria from AstraZeneca, Amgen, Roche\/Genentech, Novartis, Daiichi Sankyo, and Pfizer; and contracted research fees from Roche, Novartis, and PUMA. The rest of the authors have no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"El \u00c1lamo IV\n                      registry is a retrospective observational study conducted under current regulations, with no informed consent required. Both the\n                      El \u00c1lamo IV\n                      registry and the current study were approved by an institutional review board.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}}]}}