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This study evaluated FZD9 protein expression in breast tumors and explored its transcriptional modulation in breast cancer cell lines exposed to cytotoxic and epigenetic agents. Immunohistochemical analysis was performed in 81 breast cancer cases representing major molecular subtypes. In parallel, breast cancer cell lines were treated with trichostatin A, 5\u2010aza\u20102\u2032\u2010deoxycytidine, cisplatin, doxorubicin, paclitaxel, and ionizing radiation, followed by quantification of FZD9 mRNA levels by RT\u2010qPCR. FZD9 protein expression was more frequent in HER2\u2010enriched tumors, cases with high Ki\u201067 index, and advanced T\u2010stage. FZD9\u2010positive tumors were associated with reduced overall survival, whereas relapse\u2010free survival showed no significant difference. Baseline FZD9 transcript levels varied substantially across cell lines, and transcriptional responses to chemotherapy, radiation, and epigenetic treatment were highly context\u2010dependent, with divergent patterns observed according to molecular background. Collectively, these findings indicate that FZD9 expression in breast cancer is heterogeneous, associated with aggressive clinicopathological features, and dynamically modulated by therapeutic exposures, supporting its consideration as an exploratory marker of tumor aggressiveness and therapy\u2010related biological responses.<\/jats:p>","DOI":"10.1111\/pin.70104","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T05:32:02Z","timestamp":1773207122000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Frizzled\u20109 Expression Is Associated With Aggressive Clinicopathological Features and Reduced Overall Survival in Invasive Breast Carcinoma"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7091-1959","authenticated-orcid":false,"given":"Daniel Rodrigues de","family":"Bastos","sequence":"first","affiliation":[{"name":"Center for Translational Research in Oncology (LIM\/24), Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina Universidade de Sao Paulo S\u00e3o Paulo Brazil"},{"name":"Facultad de Ciencias M\u00e9dicas Universidad Privada del Este filial Ciudad del Este  Paraguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo Cesar","family":"Cintra","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Oncology (LIM\/24), Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina Universidade de Sao Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5779-9752","authenticated-orcid":false,"given":"Adhemar","family":"Longatto\u2010Filho","sequence":"additional","affiliation":[{"name":"Medical Laboratory of Medical Investigation (LIM\/14), Department of Pathology S\u00e3o Paulo University Faculty of Medicine S\u00e3o Paulo Brazil"},{"name":"Life and Health Sciences Research Institute (ICVS) Minho University Braga Portugal"},{"name":"Teaching and Research Institute, Molecular Oncology Research Center Barretos Cancer Hospital\u2014Pio XII Foundation S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lara","family":"Termini","sequence":"additional","affiliation":[{"name":"Center for Translational Research in Oncology (LIM\/24), Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina Universidade de Sao Paulo S\u00e3o Paulo Brazil"},{"name":"Comprehensive Center for Precision Oncology (C2PO) Universidade de Sao Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_9_3_1","unstructured":"Estat\u00edsticas de c\u00e2ncer\u2014Instituto Nacional de C\u00e2ncer\u2014INCA accessed 27 Jun 2025 https:\/\/www.gov.br\/inca\/pt-br\/assuntos\/cancer\/numeros."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.4137\/CMO.S34537"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1321654"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2011-S1-61"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-7-127"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191367098"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.05.023"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0180558"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19051543"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.3.465"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.201900490"},{"key":"e_1_2_9_14_1","first-page":"57","article-title":"Upregulation of SOX\u20102, FZD9, Nestin, OCT\u20104 and FGF\u20104 Expression in Human Chorion Derived\u2010Stem Cells After Angiogenic Induction","volume":"63","author":"Abdul","year":"2008","journal-title":"Medical Journal of Malaysia"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104442"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084232"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2006.00770.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/SREP28519"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.560074"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.4274\/ejbh.2020.5804"},{"key":"e_1_2_9_21_1","unstructured":"A.Kassambara Survminer: Drawing Survival Curves using 'ggplot2'. 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