{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T19:33:45Z","timestamp":1768764825923,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"crossref","award":["408588\/2025-0"],"award-info":[{"award-number":["408588\/2025-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"crossref","award":["303076\/2025-9"],"award-info":[{"award-number":["303076\/2025-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Secretariat of Science, Technology, and Higher Education of the State of Paran\u00e1","award":["220\/2024"],"award-info":[{"award-number":["220\/2024"]}]},{"DOI":"10.13039\/501100004612","name":"Funda\u00e7\u00e3o Arauc\u00e1ria","doi-asserted-by":"crossref","award":["147\/2025"],"award-info":[{"award-number":["147\/2025"]}],"id":[{"id":"10.13039\/501100004612","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004612","name":"Funda\u00e7\u00e3o Arauc\u00e1ria","doi-asserted-by":"crossref","award":["08\/2025"],"award-info":[{"award-number":["08\/2025"]}],"id":[{"id":"10.13039\/501100004612","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Itaipu Binacional","award":["4500007500\/2024"],"award-info":[{"award-number":["4500007500\/2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: Breast cancer is the most common neoplasm among women and remains the leading cause of cancer-related mortality in the female population worldwide. Tumor cells exist within a highly oxidative microenvironment, which promotes the formation of substantial amounts of lipid peroxides. However, the clinical significance of circulating lipid peroxides in breast cancer is still not well understood. Methods: In this study, we quantified systemic lipid peroxide levels in plasma samples from 408 breast cancer patients and examined their associations with key clinicopathological parameters to evaluate their potential as disease biomarkers. Data are reported as relative light units (RLU). Results: Our findings revealed significantly higher lipid peroxide levels in HER2-amplified tumors compared with estrogen-receptor-positive tumors (1,133,494 \u00b1 102,409 RLU vs. 951,883 \u00b1 47,535 RLU; p = 0.0438). Elevated levels were also observed in patients with triple-negative breast cancer relative to those with Luminal A (1,163,323 \u00b1 109,640 RLU vs. 875,633 \u00b1 49,601 RLU; p = 0.0356) and Luminal B tumors (1,163,323 \u00b1 109,640 RLU vs. 1,071,779 \u00b1 98,329 RLU; p = 0.0254). In addition, increased lipid peroxidation was detected in patients with high-grade tumors (G3: 1,141,035 \u00b1 101,045 RLU vs. G1\u2013G2: 949,658 \u00b1 46,119 RLU; p = 0.0346) and in those classified as at high risk of recurrence or death compared with low-risk patients (1,209,530 \u00b1 95,396 RLU vs. 978,318 \u00b1 229,526 RLU; p = 0.0054). Overweight patients also exhibited higher lipid peroxide levels than eutrophic individuals (1,131,233 \u00b1 59,633 RLU vs. 820,772 \u00b1 57,653 RLU; p = 0.0142). Conclusions: Collectively, these results suggest that circulating lipid peroxides may serve as potential biomarkers for recurrence and death risk in breast cancer, particularly among patients with more aggressive tumor phenotypes.<\/jats:p>","DOI":"10.3390\/medsci14010043","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:39:37Z","timestamp":1768563577000},"page":"43","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Lipid Peroxides Associate with More Aggressive Tumor Phenotypes and Increased Risks of Recurrence and Mortality in Breast Cancer Patients"],"prefix":"10.3390","volume":"14","author":[{"given":"Julia Fernandes Gois","family":"Orrut\u00e9a","sequence":"first","affiliation":[{"name":"Laboratory of Tumor Biology, Western Paran\u00e1 State University, Francisco Beltr\u00e3o 85605-010, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafaela Oliveira","family":"Matos","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Biology, Western Paran\u00e1 State University, Francisco Beltr\u00e3o 85605-010, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Paulo Ara\u00fajo","family":"Pinto","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Biology, Western Paran\u00e1 State University, Francisco Beltr\u00e3o 85605-010, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9 Cherubini","family":"Cechinel","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Biology, Western Paran\u00e1 State University, Francisco Beltr\u00e3o 85605-010, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruna Yukie","family":"Koizumi","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Biology, Western Paran\u00e1 State University, Francisco Beltr\u00e3o 85605-010, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael Gomes","family":"Paz","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Biology, Western Paran\u00e1 State University, Francisco Beltr\u00e3o 85605-010, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafaella Frederico","family":"Almeida","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Biology, Western Paran\u00e1 State University, Francisco Beltr\u00e3o 85605-010, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana\u00edna Carla","family":"da Silva","sequence":"additional","affiliation":[{"name":"Departamente de Biochemistry and Molecular Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3T 1J4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4634-360X","authenticated-orcid":false,"given":"Tatiane Renata","family":"Fagundes","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Biology, Western Paran\u00e1 State University, Francisco Beltr\u00e3o 85605-010, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Rech","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Biology, Western Paran\u00e1 State University, Francisco Beltr\u00e3o 85605-010, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9014-6120","authenticated-orcid":false,"given":"Guilherme","family":"Welter Wendt","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Applied Health Sciences, Western Paran\u00e1 State University, Francisco Beltr\u00e3o 85601-010, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Panis","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Biology, Western Paran\u00e1 State University, Francisco Beltr\u00e3o 85605-010, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,16]]},"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. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5906","DOI":"10.1097\/MS9.0000000000003687","article-title":"Inflammatory blood markers in breast cancer: A narrative review from early detection to therapy response","volume":"87","author":"Obeagu","year":"2025","journal-title":"Ann. Med. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4646","DOI":"10.3390\/cimb46050282","article-title":"Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production","volume":"46","author":"Dyachenko","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_4","unstructured":"Halliwell, B., and Gutteridge, J.M. (2007). Free Radicals in Biology and Medicine, Oxford University."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6429812","DOI":"10.1155\/2016\/6429812","article-title":"Can breast tumors affect the oxidative status of the surrounding environment? A comparative analysis among cancerous breast, mammary adjacent tissue, and plasma","volume":"2016","author":"Panis","year":"2016","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"168","DOI":"10.4103\/njcp.njcp_310_20","article-title":"Evaluation of biomarkers of oxidative stress and female reproductive hormones in post menopausal women with breast cancer in Southern Nigeria","volume":"24","author":"Usoro","year":"2021","journal-title":"Niger. J. Clin. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.clbc.2014.05.002","article-title":"Impact of tumor removal on the systemic oxidative profile of patients with breast cancer discloses lipid peroxidation at diagnosis as a putative marker of disease recurrence","volume":"14","author":"Herrera","year":"2014","journal-title":"Clin. Breast Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1080\/03009734.2017.1403522","article-title":"Redox status in the sentinel lymph node of women with breast cancer","volume":"122","year":"2017","journal-title":"Ups. J. Med. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.clinbiochem.2010.08.009","article-title":"Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages after chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide","volume":"43","year":"2010","journal-title":"Clin. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s10549-011-1693-x","article-title":"Oxidative stress and hematological profiles of advanced breast cancer patients subjected to paclitaxel or doxorubicin chemotherapy","volume":"133","author":"Panis","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1093\/annonc\/mdr304","article-title":"Strategies for subtypes\u2014Dealing with the diversity of breast cancer: Highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer","volume":"22","author":"Goldhirsch","year":"2011","journal-title":"Ann. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur. J. Cancer."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0891-5849(91)90002-K","article-title":"Hydroperoxide-initiated chemiluminescence: An assay for oxidative stress in biopsies of heart, liver, and muscle","volume":"10","author":"Flecha","year":"1991","journal-title":"Free Radic. Biol. Med."},{"key":"ref_14","first-page":"100598","article-title":"Changes in systemic oxidative stress correlate to chemoresistance and poor prognosis features in women with breast cancer","volume":"37","author":"Alves","year":"2024","journal-title":"Rev. Senol. Patol. Mamar."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100059","DOI":"10.1016\/j.crimmu.2023.100059","article-title":"Excess body weight significantly affects systemic and tumor inflammatory status and correlates to poor prognosis parameters in patients with breast cancer","volume":"4","author":"Silva","year":"2023","journal-title":"Curr. Res. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s12013-011-9320-3","article-title":"Quantitative redox biology: An approach to understand the role of reactive species in defining the cellular redox environment","volume":"67","author":"Buettner","year":"2013","journal-title":"Cell Biochem. Biophys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ctrv.2017.06.005","article-title":"Evolution of anti-HER2 therapies for cancer treatment","volume":"59","author":"Parakh","year":"2017","journal-title":"Cancer Treat. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Santos, L.L., Silva, A.T., Ferreira, I.C., Souza, A.V., Justino, A.B., Santos, D.W., Goulart, L.R., Paiva, C.E., Esp\u00edndola, F.S., and Maia, Y.C. (2022). A lower serum antioxidant capacity as a distinctive feature for women with HER2+ breast cancer: A Preliminary Study. Cancers, 14.","DOI":"10.3390\/cancers14235973"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/ncomms2236","article-title":"Receptor tyrosine kinase ErbB2 translocates into mitochondria and regulates cellular metabolism","volume":"3","author":"Ding","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"E14174","DOI":"10.1111\/eci.14174","article-title":"Mitochondrial HER 2 stimulates respiration and promotes tumorigenicity","volume":"54","author":"Novotna","year":"2024","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.4161\/cbt.4.12.2233","article-title":"Cross talk between mitochondria and superoxide generating NADPH oxidase in breast and ovarian tumors","volume":"4","author":"Desouki","year":"2005","journal-title":"Cancer Biol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103609","DOI":"10.1016\/j.redox.2025.103609","article-title":"Interaction between redox regulation, immune activation, and response to treatment in HER2+ breast cancer","volume":"82","author":"Luz","year":"2025","journal-title":"Redox. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/modpathol.2010.200","article-title":"Basal-like and triple-negative breast cancers: A critical review with an emphasis on the implications for pathologists and oncologists","volume":"24","author":"Badve","year":"2011","journal-title":"Mod. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1186\/s13058-014-0434-6","article-title":"Mitochondrial respiration defects in cancer cells cause activation of Akt survival pathway through a redox-mediated mechanism","volume":"16","author":"Pelicano","year":"2014","journal-title":"Breast Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sarmiento-Salinas, F.L., Delgado-Magall\u00f3n, A., Montes-Alvarado, J.B., Ram\u00edrez-Ram\u00edrez, D., Flores-Alonso, J.C., Cort\u00e9s-Hern\u00e1ndez, P., Reyes-Leyva, J., Herrera-Camacho, I., Anaya-Ruiz, M., and Pelayo, R. (2019). Breast Cancer Subtypes Present a Differential Production of Reactive Oxygen Species (ROS) and Susceptibility to Antioxidant Treatment. Front. Oncol., 7.","DOI":"10.3389\/fonc.2019.00480"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41419-021-04486-x","article-title":"Targeting prooxidant MnSOD effect inhibits triple-negative breast cancer (TNBC) progression and M2 macrophage functions under the oncogenic stress","volume":"13","author":"Tseng","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4475","DOI":"10.1245\/s10434-020-08608-1","article-title":"Molecular Biological Features of Nottingham Histological Grade 3 Breast Cancers","volume":"27","author":"Takahashi","year":"2020","journal-title":"Ann. Surg. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1038\/modpathol.3800161","article-title":"Prognostic relevance of histological grade and its components in node-negative breast cancer patients","volume":"17","author":"Volpi","year":"2004","journal-title":"Mod. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12964-023-01398-5","article-title":"Interplay of oxidative stress, cellular communication and signaling pathways in cancer","volume":"22","author":"Iqbal","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"100108","DOI":"10.1016\/j.cstres.2025.100108","article-title":"Reactive oxygen species in cancer: Mechanistic insights and therapeutic innovations","volume":"30","author":"Tan","year":"2025","journal-title":"Cell Stress. Chaperones"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Iqubal, A., and Haque, S.E. (2022). Molecular Mechanism of Oxidative Stress in Cancer and Its Therapeutics. Handbook of Oxidative Stress in Cancer: Therapeutic Aspects, Springer.","DOI":"10.1007\/978-981-16-5422-0_150"},{"key":"ref_32","unstructured":"Ministry of Health (2024). Clinical Protocol and Therapeutic Guidelines\u2014Breast Cancer, Federal District."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/ijc.10099","article-title":"Oxidant-antioxidant status in relation to survival among breast cancer patients","volume":"97","author":"Saintot","year":"2002","journal-title":"Int. J. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1172\/JCI21625","article-title":"Increased oxidative stress in obesity and its impact on metabolic syndrome","volume":"114","author":"Furukawa","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"378","DOI":"10.3390\/ijms16010378","article-title":"Oxidative stress in obesity: A critical component in human diseases","volume":"16","author":"Marseglia","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_36","first-page":"697521","article-title":"The role of chronic inflammation in obesity-associated cancers","volume":"2013","year":"2013","journal-title":"Int. Sch. Res. Not."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.3390\/ijms12053117","article-title":"Inflammation, oxidative stress, and obesity","volume":"12","author":"Bautista","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Glassman, I., Le, N., Asif, A., Goulding, A., Alcantara, C.A., Vu, A., Chorbajian, A., Mirhosseini, M., Singh, M., and Venketaraman, V. (2023). The Role of Obesity in Breast Cancer Pathogenesis. Cells, 12.","DOI":"10.3390\/cells12162061"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"789174","DOI":"10.1155\/2012\/789174","article-title":"Insulin resistance and cancer risk: An overview of the pathogenetic mechanisms","volume":"2012","author":"Arcidiacono","year":"2012","journal-title":"Exp. Diabetes Res."}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/1\/43\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T05:23:55Z","timestamp":1768713835000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/1\/43"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,16]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["medsci14010043"],"URL":"https:\/\/doi.org\/10.3390\/medsci14010043","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,16]]}}}