ArticleResearch square2023
Molecular Features of Androgen-Receptor Low, Estrogen Receptor-Negative Breast Cancers in the Carolina Breast Cancer Study.
Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 authors at 3 institutions in 1 country.
Funding
Abstract
purposeAndrogen receptor (AR) expression is absent in 40-90% of estrogen receptor (ER)-negative breast cancers. The prognostic value of AR in ER-negative patients and therapeutic targets for patients absent in AR remains poorly explored.
methodsWe used an RNA-based multigene classifier to identify AR-low and AR-high ER-negative participants in the Carolina Breast Cancer Study (CBCS; n=669) and The Cancer Genome Atlas (TCGA; n=237). We compared AR-defined subgroups by demographics, tumor characteristics, and established molecular signatures [PAM50 risk of recurrence (ROR), homologous recombination deficiency (HRD), and immune response].
resultsAR-low tumors were more prevalent among Black (relative frequency difference (RFD) = +7%, 95% CI = 1% to 14%) and younger (RFD = +10%, 95% CI = 4% to 16%) participants in CBCS and were associated with HER2-negativity (RFD = -35%, 95% CI = -44% to -26%), higher grade (RFD = +17%, 95% CI = 8% to 26%), and higher risk of recurrence scores (RFD = +22%, 95% CI = 16.1% to 28%), with similar results in TCGA. The AR-low subgroup was strongly associated with HRD in CBCS (RFD = +33.3%, 95% CI = 23.8% to 43.2%) and TCGA (RFD = +41.5%, 95% CI = 34.0% to 48.6%). In CBCS, AR-low tumors had high adaptive immune marker expression.
conclusionMultigene, RNA-based low AR expression is associated with aggressive disease characteristics as well as DNA repair defects and immune phenotypes, suggesting plausible precision therapies for AR-low, ER-negative patients.
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