{"doi":"10.1093/narcan/zcac018","title":"Luminal androgen receptor breast cancer subtype and investigation of the microenvironment and neoadjuvant chemotherapy response","abstract":"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 novel genomic classifier, LAR-Sig, that distinguishes the LAR subtype from other TNBC subtypes and provide evidence that it is a clinically distinct disease. A meta-analysis of seven TNBC datasets (n = 1086 samples) from neoadjuvant clinical trials demonstrated that LAR patients have significantly reduced response (pCR) rates than non-LAR TNBC 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 may 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. In summary, the lower levels of tumor infiltrating lymphocytes (TILs), reduced 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":"NAR Cancer","year":2022,"id":240979,"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":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.93,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":570244,"name":"Roberto A. Leon‐Ferre","orcid":"0000-0003-0594-4441","position":1,"is_corresponding":false},{"id":72551,"name":"Jason P. Sinnwell","orcid":"0000-0003-1964-5522","position":2,"is_corresponding":false},{"id":388472,"name":"David Zahrieh","orcid":"0000-0003-0529-5146","position":3,"is_corresponding":false},{"id":400209,"name":"Vera J. Suman","orcid":"0000-0002-9640-5189","position":4,"is_corresponding":false},{"id":869552,"name":"Filho Otto Metzger","orcid":null,"position":5,"is_corresponding":false},{"id":826987,"name":"Sarah Asad","orcid":"0000-0003-2759-6716","position":6,"is_corresponding":false},{"id":38074,"name":"Daniel G. Stover","orcid":"0000-0001-9003-8165","position":7,"is_corresponding":false},{"id":249118,"name":"Lisa A. Carey","orcid":"0000-0003-2388-4649","position":8,"is_corresponding":false},{"id":394927,"name":"William M. Sikov","orcid":"0000-0001-5451-6449","position":9,"is_corresponding":false},{"id":299475,"name":"James N. Ingle","orcid":"0000-0003-1257-7731","position":10,"is_corresponding":false},{"id":242419,"name":"Minetta C. Liu","orcid":"0000-0002-8206-5232","position":11,"is_corresponding":false},{"id":400214,"name":"Jodi M. Carter","orcid":"0000-0002-5973-0732","position":12,"is_corresponding":false},{"id":242575,"name":"Eric W. Klee","orcid":"0000-0003-2946-5795","position":13,"is_corresponding":false},{"id":270363,"name":"Richard M. Weinshilboum","orcid":"0000-0002-4911-7985","position":14,"is_corresponding":false},{"id":242408,"name":"Judy C. Boughey","orcid":"0000-0003-3820-3228","position":15,"is_corresponding":false},{"id":228987,"name":"Liewei Wang","orcid":"0000-0003-3818-8531","position":16,"is_corresponding":false},{"id":55313,"name":"Fergus J. Couch","orcid":"0000-0001-9417-9985","position":17,"is_corresponding":false},{"id":232394,"name":"Matthew P. Goetz","orcid":"0000-0002-4383-270X","position":18,"is_corresponding":false},{"id":329655,"name":"Krishna R. Kalari","orcid":"0000-0001-8944-8378","position":19,"is_corresponding":false},{"id":869145,"name":"Kevin J. Thompson","orcid":"0000-0002-9348-4686","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T00:22:51.435773Z","pmid":"35734391","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":[]}