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Robust and interpretable PAM50 reclassification exhibits survival advantage for myoepithelial and immune phenotypes

Author(s): Mathews, James C; Nadeem, Saad; Levine, Arnold J; Pouryahya, Maryam; Deasy, Joseph O; et al

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Abstract: We introduce a classification of breast tumors into seven classes which are more clearly defined by interpretable mRNA signatures along the PAM50 gene set than the five traditional PAM50 intrinsic subtypes. Each intrinsic subtype is partially concordant with one of our classes, and the two additional classes correspond to division of the classes concordant with the Luminal B and the Normal intrinsic subtypes along expression of the Her2 gene group. Our Normal class shows similarity with the myoepithelial mammary cell phenotype, including TP63 expression (specificity: 80.8% and sensitivity: 82.8%), and exhibits the best overall survival (89.6% at 5 years). Though Luminal A tumors are traditionally considered the least aggressive, our analysis shows that only the Luminal A tumors which are now classified as myoepithelial have this phenotype, while tumors in our luminal class (concordant with Luminal A) may be more aggressive than previously thought. We also find that patients with basal tumors surviving to 48 months exhibit favorable continued survival rates when certain markers for B lymphocytes are present and poor survival rates when they are absent, which is consistent with recent findings.
Publication Date: Jan-2019
Electronic Publication Date: 9-Sep-2019
Citation: Mathews, James C, Nadeem, Saad, Levine, Arnold J, Pouryahya, Maryam, Deasy, Joseph O, Tannenbaum, Allen. (2019). Robust and interpretable PAM50 reclassification exhibits survival advantage for myoepithelial and immune phenotypes.. NPJ breast cancer, 5 (30 - ?. doi:10.1038/s41523-019-0124-8
DOI: doi:10.1038/s41523-019-0124-8
ISSN: 2374-4677
EISSN: 2374-4677
Pages: 30 - 30
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: NPJ Breast Cancer
Version: Final published version. This is an open access article.

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