Luminal androgen receptor breast cancer subtype and investigation of the microenvironment and neoadjuvant chemotherapy response. Issue 2 (17th June 2022)

• Record Type: Journal Article
• Authors: Thompson, Kevin J; Leon-Ferre, Roberto A; Sinnwell, Jason P; Zahrieh, David M; Suman, Vera J; Metzger, Filho Otto; Asad, Sarah; Stover, Daniel G; Carey, Lisa; Sikov, William M; Ingle, James N; Liu, Minetta C; Carter, Jodi M; Klee, Eric W; Weinshilboum, Richard M; Boughey, Judy C; Wang, Liewei; Couch, Fergus J; Goetz, Matthew P; Kalari, Krishna R
• Is Part Of: NAR cancer. Volumer 4:Issue 2(2022)
• Publication Date: 2022-06-17
• Subjects: Cancer -- Periodicals; Cancer -- Genetic aspects -- Periodicals; Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 616.994
• DOI: 10.1093/narcan/zcac018
• Languages: English
• ISSNs: 2632-8674

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. Graphical Abstract: