Abstract
Background
Triple-negative breast cancer (TNBC) is a heterogeneous tumor lacking specific therapeutic targets. Several TNBC classifications have been identified using gene expression profiles, but they are difficult to use in clinical practice. In this study, we have developed a TNBC surrogate subtype classification that represents TNBC subtypes based on the Vanderbilt subtype classification.
Methods
This study included patients who underwent primary curative breast cancer surgery for TNBC between January 2009 and October 2017 at Seoul St. Mary’s Hospital. Representative formalin-fixed paraffin embedded blocks were used for gene expression analysis and tissue microarray construction for immunohistochemical (IHC) staining. The Vanderbilt subtypes were re-classified into 4 groups: basal-like (BL), mesenchymal-like (M), immunomodulatory (IM) and luminal androgen receptor (LAR) subtype. After IHC staining, classification and regression tree (CART) modeling was applied to develop a surrogate subtype classification.
Results
A total of 145 patients were included in this study. 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%). The performance of the surrogate subtypes to predict TNBC Vanderbilt 4 subtypes was good with an accuracy of 0.708. Each subtype exhibited distinct clinicopathologic features, and the M subtype showed a significantly worse survival rate than the other subtypes.
Conclusions
In this study, we have developed a TNBC surrogate subtype classification that correlates with the Vanderbilt subtype adopting AR, TIL and p16. The surrogate subtype classification is a practical and accessible diagnostic test, that can be easily applied in clinical practice.