{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T08:35:16Z","timestamp":1771403716268,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016047","name":"Science Fund of the Republic of Serbia","doi-asserted-by":"publisher","award":["PRISMA No.5050"],"award-info":[{"award-number":["PRISMA No.5050"]}],"id":[{"id":"10.13039\/501100016047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000921","name":"COST","doi-asserted-by":"publisher","award":["CA19105"],"award-info":[{"award-number":["CA19105"]}],"id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health (MH), Czech Republic","award":["MH CZ-DRO (FNOl, 00098892)"],"award-info":[{"award-number":["MH CZ-DRO (FNOl, 00098892)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aromatase inhibitors (AIs) are the standard adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer; however, their effects on lipid metabolism remain incompletely characterized. In this study, we investigated AI-associated alterations in the plasma lipidome using mass spectrometry-based lipidomics. Plasma samples were collected from 30 patients prior to AI initiation and 29 patients receiving non-steroidal AI therapy for at least 24 months. Ultra-high-performance liquid chromatography\u2013tandem mass spectrometry identified and relatively quantified 649 lipid species across 23 lipid classes and subclasses. Lipidomic analysis revealed significant differences in specific lipid species. Several phosphatidylcholine, sphingomyelin, and lysophosphatidylethanolamine species were significantly more abundant in patient plasma prior to AI therapy, whereas higher levels of selected ceramides, hexosylceramides, phosphatidylinositol (PI 16:0_16:0), and a polyunsaturated diacylglycerol species were observed in patients receiving AI therapy. Multivariate analyses revealed patient group separation, and a Naive Bayes classification model based on lipid-class levels achieved an area under the curve of 0.79. Additionally, lipid network and hierarchical clustering analyses identified systematic lipid-class trends. Protein\u2013protein interaction network analysis based on lipidomic profiles highlighted enzymes associated with sphingolipid metabolism pathways. These findings demonstrate that long-term AI therapy is associated with specific alterations in the plasma lipidome, consistent with estrogen-deprivation-related metabolic differences. Targeted lipidomic profiling may provide mechanistic insights into therapy-associated metabolic effects and support future efforts to optimize long-term management of breast cancer survivors.<\/jats:p>","DOI":"10.3390\/ijms27041926","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T13:15:35Z","timestamp":1771334135000},"page":"1926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aromatase Inhibitor Therapy Is Associated with Distinct Plasma Lipidomic Profiles in Postmenopausal Breast Cancer Patients"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8498-9415","authenticated-orcid":false,"given":"Aleksandra","family":"Arsic","sequence":"first","affiliation":[{"name":"Group for Nutritional Biochemistry and Dietology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5973-316X","authenticated-orcid":false,"given":"Ales","family":"Kvasnicka","sequence":"additional","affiliation":[{"name":"Laboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palack\u00fd University Olomouc, 779 00 Olomouc, Czech Republic"},{"name":"Department of Medical Biochemistry, Oslo University Hospital, 0372 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3448-9073","authenticated-orcid":false,"given":"David","family":"Friedecky","sequence":"additional","affiliation":[{"name":"Laboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palack\u00fd University Olomouc, 779 00 Olomouc, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nebojsa","family":"Ivanovic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Department of Surgical Oncology, University Hospital Medical Center \u201cBezanijska Kosa\u201d, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0985-0728","authenticated-orcid":false,"given":"Maja","family":"Milosevic","sequence":"additional","affiliation":[{"name":"Group for Nutritional Biochemistry and Dietology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8563-594X","authenticated-orcid":false,"given":"Vesna","family":"Vucic","sequence":"additional","affiliation":[{"name":"Group for Nutritional Biochemistry and Dietology, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"ref_1","first-page":"229","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 Cancer J. 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