Comparison of basal-like triple-negative breast cancer defined by morphology, immunohistochemistry and transcriptional profiles

Abstract

Basal-like invasive breast cancer is an important clinical group because of its association with a triple-negative phenotype defined by the lack of expression of estrogen, progesterone and human epidermal growth factor receptors 2, relative lack of therapeutic options and poor prognosis. However, depending on the method used to define these lesions, morphological assessment, immunohistochemical markers or gene expression, a different set of tumors is captured. The aim of this study was to investigate the consequences of using different methodological approaches to define basal-like lesions among triple-negative breast carcinomas with regard to their clinicopathological features and patient outcome. The cohort consisted of 142 invasive breast cancers with a triple-negative receptor status. First, each was reviewed histologically and those with morphological basallike features were characterized as 'Path-Basal'. Second, the 'Core Basal' immunohistochemical lesions, defined as cytokeratin 5/6 and/or epidermal growth factor receptor 1 positive, within the triple-negative breast cancers were identified, and third their classification based on gene expression profiling was retrieved and those in the molecular 'PAM50 basal-like' subtype recorded. A total of 116 basal-like breast cancers were identified among the 142 triple-negative breast cancers by at least one of these three classifications (80%), but only 13 samples were defined as basal-like with all three methods. None of these 13 tumors were associated with lymphovascular invasion. The 34 morphological 'Path-Basal' lesions were significantly associated with a lack of nodal metastases. Comparing the estimates of death in the three classifications, the highest risk of death was seen for the 'Core Basal' group. In this study, we highlight that the definition of basal-like breast cancer based on different methodologies varies significantly and does not identify the same lesions. This incomplete overlap of cases emphasizes the need for consistent or new approaches to improve precise identification. Modern Pathology (2013) 26, 955-966;

IL15RA Drives Antagonistic Mechanisms of Cancer Development and Immune Control in Lymphocyte-Enriched Triple-Negative Breast Cancers

“…Investigating the copy number of chromosome 10 in our Guy's TNBC-enriched BC cohort (27), using Affymetrix SNP6.0-derived genomic profiles, we confirmed the presence of an amplicon encompassing approximately 10 Mbp of the most distal region of the short arm of chromosome 10 (10:82,824-8,738,800; hg18). Within this amplicon, a number of genes had an absolute copy number of greater than 4 in at least 30% of TNBC cases ( Fig.…”

“…The Tumor Aberration Prediction Suite algorithm (22) (25,26). PAM50 classification was as described for the Guy's (27), METABRIC (23), and TCGA cohorts (6). TNBC subtypes were established using the online TNBC-type program (28).…”

Recent Progress in Triple Negative Breast Cancer Research

“…It usually associated with very aggressive clinical behaviors and is more prevalent in cases with distinctive metastatic patterns (Gazinska et al, 2013). …”

Triple Negative Breast Cancer Pathologic Diagnosis and Current Chemotherapy Treatment Options

“…In this study by Gazinska et al, 8 those TNBC that were positive for CK5/6 and/or EGFR were designated as core basal, those with pathologic criteria were designated as path-basal, and those designated according to molecular profiling (PAM50) were designated as PAM50 BL. 9 The non-core BL carcinomas may also be designated as 5-marker negative panel (5NP).…”