Luminal androgen receptor breast cancer subtype and investigation of the microenvironment and neoadjuvant chemotherapy response

Kevin J. Thompson, Roberto A. Leon-Ferre, Jason P. Sinnwell, David M. Zahrieh, Vera J. Suman, Filho Otto Metzger, Sarah Asad, Daniel G. Stover, Lisa Carey, William M. Sikov, James N. Ingle, Minetta C Liu, Jodi Carter, Eric W. Klee, Richard M. Weinshilboum, Judy C. Boughey, Liewei M Wang, Fergus J. Couch, Matthew Philip Goetz, Krishna R. Kalari

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numberzcac018
JournalNAR Cancer
Issue number2
StatePublished - Jun 1 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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