{"doi":"10.17615/h225-mq92","title":"Luminal androgen receptor breast cancer subtype and investigation of the microenvironment and neoadjuvant chemotherapy response","abstract":"Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with low overall survival rates and high molecular heterogeneity; therefore, few targeted therapies are available. The luminal androgen receptor (LAR) is the most consistently identified TNBC subtype, but the clinical utility has yet to be established. Here, we constructed a&nbsp;novel&nbsp;genomic classifier, LAR-Sig, that distinguishes the LAR subtype from other TNBC subtypes&nbsp;and provide&nbsp;evidence that it is a clinically distinct disease. A&nbsp;meta-analysis of&nbsp;seven TNBC&nbsp;datasets (<em>n</em> = 1086 samples) from neoadjuvant clinical trials demonstrated&nbsp;that LAR patients have significantly reduced response (pCR) rates than non-LAR TNBC&nbsp;patients (odds ratio = 2.11, 95% CI: 1.33, 2.89). Moreover, deconvolution of the tumor microenvironment confirmed an enrichment of luminal epithelium corresponding with a decrease in basal and myoepithelium in LAR TNBC tumors. Increased immunosuppression in LAR patients&nbsp;may&nbsp;lead to a decreased presence of cycling T-cells and plasma cells. While, an increased presence of myofibroblast-like cancer-associated cells may impede drug delivery and treatment.&nbsp;In summary, the lower levels of tumor infiltrating lymphocytes (TILs), reduced&nbsp;immune activity in the micro-environment, and lower pCR rates after NAC, suggest that new therapeutic strategies for the LAR TNBC subtype need to be developed.","journal":"UNC Libraries","year":2025,"id":560761,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7782,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":38074,"name":"Daniel G. Stover","orcid":"0000-0001-9003-8165","position":1,"is_corresponding":false},{"id":388472,"name":"David Zahrieh","orcid":"0000-0003-0529-5146","position":2,"is_corresponding":false},{"id":232394,"name":"Matthew P. Goetz","orcid":"0000-0002-4383-270X","position":3,"is_corresponding":false},{"id":242575,"name":"Eric W. Klee","orcid":"0000-0003-2946-5795","position":4,"is_corresponding":false},{"id":249118,"name":"Lisa A. Carey","orcid":"0000-0003-2388-4649","position":5,"is_corresponding":false},{"id":228987,"name":"Liewei Wang","orcid":"0000-0003-3818-8531","position":6,"is_corresponding":false},{"id":400209,"name":"Vera J. Suman","orcid":"0000-0002-9640-5189","position":7,"is_corresponding":false},{"id":55313,"name":"Fergus J. Couch","orcid":"0000-0001-9417-9985","position":8,"is_corresponding":false},{"id":270363,"name":"Richard M. Weinshilboum","orcid":"0000-0002-4911-7985","position":9,"is_corresponding":false},{"id":394927,"name":"William M. Sikov","orcid":"0000-0001-5451-6449","position":10,"is_corresponding":false},{"id":72551,"name":"Jason P. Sinnwell","orcid":"0000-0003-1964-5522","position":11,"is_corresponding":false},{"id":329655,"name":"Krishna R. Kalari","orcid":"0000-0001-8944-8378","position":12,"is_corresponding":false},{"id":826987,"name":"Sarah Asad","orcid":"0000-0003-2759-6716","position":13,"is_corresponding":false},{"id":869552,"name":"Filho Otto Metzger","orcid":null,"position":14,"is_corresponding":false},{"id":242408,"name":"Judy C. Boughey","orcid":"0000-0003-3820-3228","position":15,"is_corresponding":false},{"id":1463146,"name":"Roberto A Leon-Ferre","orcid":null,"position":16,"is_corresponding":false},{"id":242419,"name":"Minetta C. Liu","orcid":"0000-0002-8206-5232","position":17,"is_corresponding":false},{"id":400214,"name":"Jodi M. Carter","orcid":"0000-0002-5973-0732","position":18,"is_corresponding":false},{"id":299475,"name":"James N. Ingle","orcid":"0000-0003-1257-7731","position":19,"is_corresponding":false},{"id":869145,"name":"Kevin J. Thompson","orcid":"0000-0002-9348-4686","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:46.921885Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}