A triple-negative breast cancer surrogate subtype classification that correlates with gene expression subtypes

Abstract

Background: This study developed a triple-negative breast cancer (TNBC) surrogate subtype classification that represents TNBC subtypes based on the Vanderbilt subtype classification.

Methods: Patients who underwent primary curative surgery for TNBC were included. Representative FFPE blocks were used for gene expression analysis and tissue microarray construction for immunohistochemical (IHC) staining. The Vanderbilt subtypes were re-classified into four groups: basal-like (BL), mesenchymal-like (M), immunomodulatory (IM) and luminal androgen receptor (LAR) subtype. Classification and regression tree (CART) modeling was applied to develop a surrogate subtype classification.

Results: A total of 145 patients were included. The study cohort was allocated to the Vanderbilt 4 subtypes as LAR (n = 22, 15.2%), IM (n = 32, 22.1%), M (n = 38, 26.2%), BL (n = 25, 17.2%) and unclassified (n = 28, 19.3%). After excluding nine (6.2%) patients due to poor IHC staining quality, CART modeling was performed. TNBC surrogate subtypes were defined as follows: LAR subtype, androgen receptor Allred score 8; IM subtype, LAR-negative with a tumor-infiltrating lymphocyte (TIL) score > 70%; M subtype, LAR-negative with a TIL score < 20%; BL subtype, LAR-negative with a TIL score 20-70% and diffuse, strong p16 staining. The study cohort was classified by the surrogate subtypes as LAR (n = 26, 17.9%), IM (n = 21, 14.5%), M (n = 44, 30.3%), BL1 (n = 27, 18.6%) and unclassified (n = 18, 12.4%). Surrogate subtypes predicted TNBC Vanderbilt 4 subtypes with an accuracy of 0.708.

Conclusion: We have developed a TNBC surrogate subtype classification that correlates with the Vanderbilt subtype. It is a practical and accessible diagnostic test that can be easily applied in clinical practice.

Keywords: Biomarkers; Classification; Cyclin-dependent kinase inhibitor p16; Lymphocytes, tumor-infiltration; Receptors, androgen; Triple-negative breast neoplasms.