{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:16:46Z","timestamp":1786112206467,"version":"build-2736575974"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The tumour microenvironment (TME) influences breast cancer progression and treatment response. We investigated whether TME composition predicts tamoxifen benefit in postmenopausal women with oestrogen receptor-positive, HER2-negative (ER+HER2-) breast cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study included 513 patients from the Stockholm Tamoxifen (STO-3) trial, which randomised postmenopausal, lymph node\u2013negative women to tamoxifen or no endocrine therapy. Bulk tumour transcriptomes were deconvoluted with the ConsensusTME algorithm to estimate the relative abundance of 18 immune and stromal cell types. A summary score of combined immune cells was created on a per patient basis and evaluated alongside fibroblast and endothelial stromal compartments. Patients were categorised into immune and stromal tertiles on the basis of these scores. Associations between TME composition and tumour characteristics were evaluated using Spearman correlations and Fisher\u2019s exact test. Tamoxifen benefit was analysed by univariable Kaplan-Meier (log-rank) and multivariable Cox proportional hazards adjusting for age, tumour size, grade, progesterone receptor, Ki-67, and radiotherapy. Differential expression was assessed with limma and pathway enrichment with fgsea using Hallmark gene sets from MSigDB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Low immune abundance was significantly associated with higher ER expression (Kruskal-Wallis test p\u2009&lt;\u20090.001). Among tamoxifen-treated patients, those with low immune scores showed improved distant recurrence-free interval (DRFI) relative to untreated patients (log-rank p\u2009&lt;\u20090.001). Similarly, intermediate endothelial (p\u2009&lt;\u20090.001) and low\/intermediate fibroblast abundances (p\u2009=\u20090.042, p\u2009=\u20090.009) were associated with favourable DRFI. In multivariable models, low immune (adjusted HR\u2009=\u20090.17, 95% CI 0.08\u20130.40), intermediate endothelial (aHR = 0.21, 95% CI 0.09\u20130.51), and low\/intermediate fibroblast tertiles (aHR = 0.50, 95% CI 0.27\u20130.93; aHR = 0.36, 95% CI 0.17\u20130.77) retained significance. Transcriptomic analysis revealed enrichment of oestrogen-response, MYC-target, and oxidative-phosphorylation pathways in low-immune and low-fibroblast tumours, while interferon-\u03b3 response and allograft rejection pathways were downregulated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TME composition modulates tamoxifen benefit in postmenopausal ER+HER2\u2212 breast cancer. Low immune, intermediate endothelial, and low\/intermediate fibroblast abundances are associated with improved benefit from tamoxifen, suggesting that both immune and stromal compartments influence endocrine treatment efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12916-026-05091-5","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:44:28Z","timestamp":1785930268000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The tumour microenvironment influences long-term tamoxifen benefit in postmenopausal ER+\/HER2\u2212 breast cancer patients: a secondary analysis of the randomised Stockholm Tamoxifen (STO-3) trial"],"prefix":"10.1186","volume":"24","author":[{"given":"Paula","family":"Camargo-Romera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Castresana\u2011Aguirre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Danielsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huma","family":"Dar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"\u00d6stman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Czene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda S.","family":"Lindstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P.","family":"Tobin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"5091_CR1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3322\/caac.21871","volume":"75","author":"RL Siegel","year":"2025","unstructured":"Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025;75:10\u201345. https:\/\/doi.org\/10.3322\/caac.21871","journal-title":"CA Cancer J Clin"},{"key":"5091_CR2","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.breast.2022.08.010","volume":"66","author":"M Arnold","year":"2022","unstructured":"Arnold M, Morgan E, Rumgay H, Mafra A, Singh D, Laversanne M, et al. Current and future burden of breast cancer: global statistics for 2020 and 2040. The Breast. 2022;66:15\u201323. https:\/\/doi.org\/10.1016\/j.breast.2022.08.010","journal-title":"The Breast"},{"key":"5091_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/S40164-022-00363-1","volume":"12","author":"L Guo","year":"2023","unstructured":"Guo L, Kong D, Liu J, Zhan L, Luo L, Zheng W, et al. Breast cancer heterogeneity and its implication in personalized precision therapy. Exp Hematol Oncol. 2023;12:1\u201327. https:\/\/doi.org\/10.1186\/S40164-022-00363-1","journal-title":"Exp Hematol Oncol"},{"key":"5091_CR4","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06110-6","volume":"14","author":"Y Zhao","year":"2023","unstructured":"Zhao Y, Shen M, Wu L, Yang H, Yao Y, Yang Q, et al. Stromal cells in the tumor microenvironment: accomplices of tumor progression? Cell Death Dis. 2023;14:587 https:\/\/doi.org\/10.1038\/s41419-023-06110-6","journal-title":"Cell Death Dis"},{"key":"5091_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/J.PHRS.2020.104683","volume":"153","author":"KGK Deepak","year":"2020","unstructured":"Deepak KGK, Vempati R, Nagaraju GP, Dasari VR, Nagini S, Rao DN, et al. Tumor microenvironment: challenges and opportunities in targeting metastasis of triple negative breast cancer. Pharmacol Res. 2020;153:104683 https:\/\/doi.org\/10.1016\/J.PHRS.2020.104683","journal-title":"Pharmacol Res"},{"key":"5091_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41597-023-02032-2","volume":"10","author":"H Zhao","year":"2023","unstructured":"Zhao H, Yin X, Wang L, Liu K, Liu W, Bo L, et al. Identifying tumour microenvironment-related signature that correlates with prognosis and immunotherapy response in breast cancer. Sci Data. 2023;10:1\u201314. https:\/\/doi.org\/10.1038\/s41597-023-02032-2","journal-title":"Sci Data"},{"key":"5091_CR7","doi-asserted-by":"publisher","first-page":"348","DOI":"10.3389\/fimmu.2019.00348","volume":"10","author":"M Segovia-Mendoza","year":"2019","unstructured":"Segovia-Mendoza M, Morales-Montor J. Immune tumor microenvironment in breast cancer and the participation of estrogens and its receptors into cancer physiopathology. Front Immunol. 2019;10:348 https:\/\/doi.org\/10.3389\/fimmu.2019.00348","journal-title":"Front Immunol"},{"key":"5091_CR8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002194","volume":"13","author":"HR Ali","year":"2016","unstructured":"Ali HR, Chlon L, Pharoah PDP, Markowetz F, Caldas C. Patterns of immune infiltration in breast cancer and their clinical implications: a gene-expression-based retrospective study. PLoS Med. 2016;13:e1002194 https:\/\/doi.org\/10.1371\/journal.pmed.1002194","journal-title":"PLoS Med"},{"key":"5091_CR9","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1200\/JCO.2010.30.5037","volume":"29","author":"SMA Mahmoud","year":"2011","unstructured":"Mahmoud SMA, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AHS, et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol. 2011;29:1949\u201355. https:\/\/doi.org\/10.1200\/JCO.2010.30.5037","journal-title":"J Clin Oncol"},{"key":"5091_CR10","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.153963","volume":"7","author":"CA Egelston","year":"2022","unstructured":"Egelston CA, Guo W, Tan J, Avalos C, Simons DL, Lim MH, et al. Tumor-infiltrating exhausted CD8+ T cells dictate reduced survival in premenopausal estrogen receptor\u2013positive breast cancer. JCI Insight. 2022;7:e153963 https:\/\/doi.org\/10.1172\/jci.insight.153963","journal-title":"JCI Insight"},{"key":"5091_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/IJMS21186968","volume":"21","author":"M Oshi","year":"2020","unstructured":"Oshi M, Asaoka M, Tokumaru Y, Yan L, Matsuyama R, Ishikawa T, et al. CD8 T cell score as a prognostic biomarker for triple negative breast cancer. Int J Mol Sci. 2020;21:1\u201316. https:\/\/doi.org\/10.3390\/IJMS21186968","journal-title":"Int J Mol Sci"},{"key":"5091_CR12","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1080\/02841860601034834","volume":"46","author":"LE Rutqvist","year":"2007","unstructured":"Rutqvist LE, Johansson H, Stockholm Breast Cancer Study Group. Long-term follow-up of the randomized Stockholm trial on adjuvant tamoxifen among postmenopausal patients with early stage breast cancer. Acta Oncol. 2007;46:133\u201345. https:\/\/doi.org\/10.1080\/02841860601034834","journal-title":"Acta Oncol"},{"key":"5091_CR13","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1093\/JNCI\/DJX270","volume":"110","author":"LS Lindstr\u00f6m","year":"2018","unstructured":"Lindstr\u00f6m LS, Yau C, Czene K, Thompson CK, Hoadley KA, Van\u2019t Veer LJ, et al. Intratumor heterogeneity of the estrogen receptor and the long-term risk of Fatal Breast Cancer. JNCI J Natl Cancer Inst. 2018;110:726\u201333. https:\/\/doi.org\/10.1093\/JNCI\/DJX270","journal-title":"JNCI J Natl Cancer Inst"},{"key":"5091_CR14","doi-asserted-by":"publisher","first-page":"2072","DOI":"10.1002\/IJC.33969","volume":"150","author":"A Johansson","year":"2022","unstructured":"Johansson A, Yu NY, Iftimi A, Tobin NP, van \u2019t Veer L, Nordenskj\u00f6ld B, et al. Clinical and molecular characteristics of estrogen receptor-positive ultralow risk breast cancer tumors identified by the 70-gene signature. Int J Cancer. 2022;150:2072\u201382. https:\/\/doi.org\/10.1002\/IJC.33969","journal-title":"Int J Cancer"},{"key":"5091_CR15","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1080\/02841860802247664","volume":"48","author":"L Barlow","year":"2009","unstructured":"Barlow L, Westergren K, Holmberg L, T\u00e4lback M. The completeness of the Swedish cancer register - a sample survey for year 1998. Acta Oncol. 2009;48:27\u201333. https:\/\/doi.org\/10.1080\/02841860802247664","journal-title":"Acta Oncol"},{"key":"5091_CR16","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1007\/s10654-017-0316-1","volume":"32","author":"HL Brooke","year":"2017","unstructured":"Brooke HL, Talb\u00e4ck M, H\u00f6rnblad J, Johansson LA, Ludvigsson JF, Druid H, et al. The Swedish cause of death register. Eur J Epidemiol. 2017;32:765\u201373. https:\/\/doi.org\/10.1007\/s10654-017-0316-1","journal-title":"Eur J Epidemiol"},{"key":"5091_CR17","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1111\/joim.12303","volume":"277","author":"L Emilsson","year":"2015","unstructured":"Emilsson L, Lindahl B, K\u00f6ster M, Lambe M, Ludvigsson JF. Review of 103 Swedish healthcare quality registries. J Intern Med. 2015;277:94\u2013136. https:\/\/doi.org\/10.1111\/joim.12303","journal-title":"J Intern Med"},{"key":"5091_CR18","unstructured":"Regionala cancercentrum i samverkan. Nationellt v\u00e5rdprogram br\u00f6stcancer. Version 16 juni 2026. Stockholm: Regionala cancercentrum i samverkan; 2026. Available from: Kunskapsbanken \u2013 Nationellt v\u00e5rdprogram br\u00f6stcancer https:\/\/kunskapsbanken.cancercentrum.se\/globalassets\/cancerdiagnoser\/brost\/vardprogram\/nationellt-vardprogram-brostcancer.pdf"},{"key":"5091_CR19","doi-asserted-by":"publisher","first-page":"1762","DOI":"10.1038\/bjc.2011.145","volume":"104","author":"PL Jerevall","year":"2011","unstructured":"Jerevall PL, Ma XJ, Li H, Salunga R, Kesty NC, Erlander MG, et al. Prognostic utility of HOXB13: IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial. Br J Cancer. 2011;104:1762\u20139. https:\/\/doi.org\/10.1038\/bjc.2011.145","journal-title":"Br J Cancer"},{"key":"5091_CR20","doi-asserted-by":"publisher","first-page":"6238","DOI":"10.1158\/0008-5472.CAN-18-3560","volume":"79","author":"A Jimenez-Sanchez","year":"2019","unstructured":"Jimenez-Sanchez A, Cast O, Miller ML. Comprehensive benchmarking and integration of tumor microenvironment cell estimation methods. Cancer Res. 2019;79:6238\u201346. 10.1158\/0008-5472.CAN-18-3560\/653647\/AM\/COMPREHENSIVE-BENCHMARKING-AND-INTEGRATION-OF","journal-title":"Cancer Res"},{"key":"5091_CR21","doi-asserted-by":"publisher","first-page":"2127","DOI":"10.1200\/JCO.2006.10.3523","volume":"25","author":"CA Hudis","year":"2007","unstructured":"Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman JAW, et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007;25:2127\u201332. https:\/\/doi.org\/10.1200\/JCO.2006.10.3523","journal-title":"J Clin Oncol"},{"key":"5091_CR22","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1200\/JCO.2007.14.3222","volume":"26","author":"F Cardoso","year":"2008","unstructured":"Cardoso F, Van\u2019t Veer L, Rutgers E, Loi S, Mook S, Piccart-Gebhart MJ. Clinical application of the 70-gene profile: The MINDACT trial. J Clin Oncol. 2008;26:729\u201335. https:\/\/doi.org\/10.1200\/JCO.2007.14.3222","journal-title":"J Clin Oncol"},{"key":"5091_CR23","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-019-1176-2","volume":"21","author":"M Sobral-Leite","year":"2019","unstructured":"Sobral-Leite M, Salomon I, Opdam M, Kruger DT, Beelen KJ, Van Der Noort V, et al. Cancer-immune interactions in ER-positive breast cancers: PI3K pathway alterations and tumor-infiltrating lymphocytes. Breast Cancer Res. 2019;21:90 https:\/\/doi.org\/10.1186\/s13058-019-1176-2","journal-title":"Breast Cancer Res"},{"key":"5091_CR24","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/jnci\/djx137","volume":"110","author":"A Heindl","year":"2017","unstructured":"Heindl A, Sestak I, Naidoo K, Cuzick J, Dowsett M, Yuan Y. Relevance of spatial heterogeneity of immune infiltration for predicting risk of recurrence after endocrine therapy of ER+ Breast Cancer. J Natl Cancer Inst. 2017;110:166\u201375. https:\/\/doi.org\/10.1093\/jnci\/djx137","journal-title":"J Natl Cancer Inst"},{"issue":"1 SUPPL","key":"5091_CR25","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s10549-007-9701-x","volume":"105","author":"MJ Ellis","year":"2007","unstructured":"Ellis MJ, Ma C. Letrozole in the neoadjuvant setting: the P024 trial. Breast Cancer Res Treat. 2007;105(1 SUPPL):33\u201343. https:\/\/doi.org\/10.1007\/s10549-007-9701-x","journal-title":"Breast Cancer Res Treat"},{"key":"5091_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2023.113473","volume":"197","author":"S Makhlouf","year":"2024","unstructured":"Makhlouf S, Quinn C, Toss M, Alsaleem M, Atallah NM, Ibrahim A, et al. Quantitative expression of oestrogen receptor in breast cancer: clinical and molecular significance. Eur J Cancer. 2024;197:113473 https:\/\/doi.org\/10.1016\/j.ejca.2023.113473","journal-title":"Eur J Cancer"},{"key":"5091_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/srep21164","volume":"6","author":"RT Bekele","year":"2016","unstructured":"Bekele RT, Venkatraman G, Liu R-Z, Tang X, Mi S, Benesch MGK, et al. Oxidative stress contributes to the tamoxifen-induced killing of breast cancer cells: implications for tamoxifen therapy and resistance. Sci Rep. 2016;6:21164 https:\/\/doi.org\/10.1038\/srep21164","journal-title":"Sci Rep"},{"key":"5091_CR28","doi-asserted-by":"publisher","first-page":"3397","DOI":"10.1158\/1078-0432.CCR-17-2551","volume":"24","author":"AEM Post","year":"2018","unstructured":"Post AEM, Smid M, Nagelkerke A, Martens JWM, Bussink J, Sweep FCGJ, et al. Interferon-stimulated genes are involved in cross-resistance to radiotherapy in tamoxifen-resistant breast cancer. Clin Cancer Res. 2018;24:3397\u2013408. https:\/\/doi.org\/10.1158\/1078-0432.CCR-17-2551","journal-title":"Clin Cancer Res"},{"key":"5091_CR29","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/nrc.2016.73","volume":"16","author":"R Kalluri","year":"2016","unstructured":"Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16:582\u201398. https:\/\/doi.org\/10.1038\/nrc.2016.73","journal-title":"Nat Rev Cancer"},{"key":"5091_CR30","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.1056\/nejmoa1609709","volume":"375","author":"GN Hortobagyi","year":"2016","unstructured":"Hortobagyi GN, Stemmer SM, Burris HA, Yap Y-S, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375:1738\u201348. https:\/\/doi.org\/10.1056\/nejmoa1609709","journal-title":"N Engl J Med"},{"key":"5091_CR31","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S1470-2045(22)00694-5","volume":"24","author":"SRD Johnston","year":"2023","unstructured":"Johnston SRD, Toi M, O\u2019Shaughnessy J, Rastogi P, Campone M, Neven P, et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24:77\u201390. https:\/\/doi.org\/10.1016\/S1470-2045(22)00694-5","journal-title":"Lancet Oncol"},{"key":"5091_CR32","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1056\/nejmoa1607303","volume":"375","author":"RS Finn","year":"2016","unstructured":"Finn RS, Martin M, Rugo HS, Jones S, Im S-A, Gelmon K, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375:1925\u201336. https:\/\/doi.org\/10.1056\/nejmoa1607303","journal-title":"N Engl J Med"},{"key":"5091_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-018-0097-z","volume":"5","author":"S Johnston","year":"2019","unstructured":"Johnston S, Martin M, Di Leo A, Im SA, Awada A, Forrester T, et al. MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. Npj Breast Cancer. 2019;5:5 https:\/\/doi.org\/10.1038\/s41523-018-0097-z","journal-title":"Npj Breast Cancer"},{"key":"5091_CR34","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/s41591-024-03415-7","volume":"31","author":"F Cardoso","year":"2025","unstructured":"Cardoso F, O\u2019Shaughnessy J, Liu Z, McArthur H, Schmid P, Cortes J, et al. Pembrolizumab and chemotherapy in high-risk, early-stage, ER+\/HER2\u2212 breast cancer: a randomized phase 3 trial. Nat Med. 2025;31:442\u20138. https:\/\/doi.org\/10.1038\/s41591-024-03415-7","journal-title":"Nat Med"},{"key":"5091_CR35","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/s41591-024-03414-8","volume":"31","author":"S Loi","year":"2025","unstructured":"Loi S, Salgado R, Curigliano G, Romero D\u00edaz RI, Delaloge S, Rojas Garc\u00eda CI, et al. Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial. Nat Med. 2025;31:433\u201341. https:\/\/doi.org\/10.1038\/s41591-024-03414-8","journal-title":"Nat Med"},{"key":"5091_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19015-1","volume":"11","author":"F Avila Cobos","year":"2020","unstructured":"Avila Cobos F, Alquicira-Hernandez J, Powell JE, Mestdagh P, De Preter K. Benchmarking of cell type deconvolution pipelines for transcriptomics data. Nat Commun. 2020;11:5650 https:\/\/doi.org\/10.1038\/s41467-020-19015-1","journal-title":"Nat Commun"},{"key":"5091_CR37","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/s43856-024-00471-5","volume":"4","author":"S Arslan","year":"2024","unstructured":"Arslan S, Schmidt J, Bass C, Mehrotra D, Geraldes A, Singhal S, et al. A systematic pan-cancer study on deep learning-based prediction of multi-omic biomarkers from routine pathology images. Commun Med. 2024;4:48 https:\/\/doi.org\/10.1038\/s43856-024-00471-5","journal-title":"Commun Med"},{"key":"5091_CR38","doi-asserted-by":"publisher","first-page":"e197700","DOI":"10.1001\/jamanetworkopen.2019.7700","volume":"2","author":"G Shamai","year":"2019","unstructured":"Shamai G, Binenbaum Y, Slossberg R, Duek I, Gil Z, Kimmel R. Artificial intelligence algorithms to assess hormonal status from tissue microarrays in patients with breast cancer. JAMA Netw Open. 2019;2:e197700 https:\/\/doi.org\/10.1001\/jamanetworkopen.2019.7700","journal-title":"JAMA Netw Open"},{"key":"5091_CR39","doi-asserted-by":"publisher","unstructured":"Johansson A, Lindstr\u00f6m L. Agilent gene expression microarray raw data for STO-3. Swedish National Data Service (SND). 2022. https:\/\/doi.org\/10.5878\/3vxa-3c28","DOI":"10.5878\/3vxa-3c28"}],"container-title":["BMC Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12916-026-05091-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-026-05091-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-026-05091-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:43:48Z","timestamp":1785941028000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12916-026-05091-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5091"],"URL":"https:\/\/doi.org\/10.1186\/s12916-026-05091-5","relation":{},"ISSN":["1741-7015"],"issn-type":[{"value":"1741-7015","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]},"assertion":[{"value":"13 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The STO trials were approved by the Karolinska Institutet Regional Ethics Committee, with the Stockholm Regional Cancer Center serving as the trial centre. Written informed consent was obtained from all participants before randomisation. The STO trial was initiated in 1976, before the practice of trial registration in Sweden; therefore, no trial registration number is available.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"424"}}