{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T19:21:23Z","timestamp":1767900083001,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T00:00:00Z","timestamp":1750464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The role of neoadjuvant endocrine therapy (NET) in patients with luminal tumors is still not well defined in everyday clinical practice. To assess the efficacy of combination NET, we analyzed the outcomes of fulvestrant and aromatase inhibitors (AI) in combination in a real-world population. Methods: This was a single-arm, retrospective longitudinal study of the total population of patients diagnosed with locoregionally advanced, clinical stage II-III, HR+ HER2-, luminal-type eBC, who were treated with the neoadjuvant combination of fulvestrant and AI between 2019 and 2024 at the Clinical University Hospital of Split, Croatia. Results: We enrolled 44 patients in the intention-to-treat (ITT) population, while 34 completed NET and surgery (per-protocol population; PPP). The median duration of NET was 11 months (interquartile range [IQR] of 9\u201316 months). The best radiological objective response rate (partial or complete response) was achieved by 30 (68.2%) in ITT, and 26 (76.5%) in PPP, defined by radiological examination, breast ultrasound, or MR. In the PPP, the minimal or moderate pathological response according to residual cancer burden (I or II) was observed in 29 (85.3%) patients. The median of absolute changes in Ki-67 was \u22125 (95% CI: \u22129 to 0), and the median of relative Ki67 changes was \u221240% (95% CI: \u221272% to 0%). Post-surgical Ki-67 was significantly predicted by initial Ki-67, positive lymph nodes, and time from diagnosis to the initiation of NET. Treatment was well tolerated, with no therapy discontinuation or dose reductions needed due to toxicity. The most commonly reported side effects included musculoskeletal pain (45.5%), asthenia (34.1%), and hot flashes (29.5%). Conclusions: Dual hormonal therapy with fulvestrant and AI is an active, easily given, non-toxic, promising neoadjuvant treatment in real-world patients with locally advanced luminal-type eBC who are not candidates for chemotherapy.<\/jats:p>","DOI":"10.3390\/cancers17132083","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T03:39:26Z","timestamp":1750649966000},"page":"2083","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy of Dual Hormonal Therapy with Fulvestrant and Aromatase Inhibitors as Neoadjuvant Endocrine Treatment for Locally Advanced Breast Cancer"],"prefix":"10.3390","volume":"17","author":[{"given":"Ana","family":"Maji\u0107","sequence":"first","affiliation":[{"name":"Department of Oncology, University Hospital Center Split, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7983-6892","authenticated-orcid":false,"given":"\u017darko","family":"Baji\u0107","sequence":"additional","affiliation":[{"name":"Research Unit \u201cDr. Mirko Grmek\u201d, Psychiatric Clinic Sveti Ivan, 10090 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Ban","sequence":"additional","affiliation":[{"name":"Department of Oncology, University Hospital Center Split, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Tica Sedlar","sequence":"additional","affiliation":[{"name":"Department of Oncology, University Hospital Center Split, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dora","family":"\u010cerina Pavlinovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Oncology, University Hospital Center Split, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Branka","family":"Petri\u0107 Mi\u0161e","sequence":"additional","affiliation":[{"name":"Department of Oncology, University Hospital Center Split, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ante","family":"Striki\u0107","sequence":"additional","affiliation":[{"name":"Department of Oncology, University Hospital Center Split, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Snje\u017eana","family":"Tomi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathology, Forensic Medicine and Cytology, Clinical Hospital Center Split, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard","family":"Vrdoljak","sequence":"additional","affiliation":[{"name":"Department of Oncology, University Hospital Center Split, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. 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