Basal-like and Triple-negative Breast Cancers

A Critical Review With an Emphasis on The Implications for Pathologists and Oncologists

Sunil Badve; David J Dabbs; Stuart J Schnitt; Frederick L Baehner; Thomas Decker; Vincenzo Eusebi; Stephen B Fox; Shu Ichihara; Jocelyne Jacquemier; Sunil R Lakhani; José Palacios; Emad A Rakha; Andrea L Richardson; Fernando C Schmitt; Puay-Hoon Tan; Gary M Tse; Britta Weigelt; Ian O Ellis; Jorge S Reis-Filho

Disclosures

Mod Pathol. 2011;24(2):157-167. 

In This Article

Abstract and Introduction

Abstract

Breast cancer is a heterogeneous disease encompassing a variety of entities with distinct morphological features and clinical behaviors. Although morphology is often associated with the pattern of molecular aberrations in breast cancers, it is also clear that tumors of the same histological type show remarkably different clinical behavior. This is particularly true for 'basal-like cancer', which is an entity defined using gene expression analysis. The purpose of this article was to review the current state of knowledge of basal-like breast cancers, to discuss the relationship between basal-like and triple-negative breast cancers, and to clarify practical implications of these diagnoses for pathologists and oncologists.

Introduction

Breast cancer is a heterogeneous disease, and this term encompasses a variety of entities with distinct morphological features and clinical behaviors. In recent years, it has become apparent that this diversity is the result of distinct genetic, epigenetic, and transcriptomic alterations.[1–5] Although morphology is often associated with the pattern of molecular aberrations in breast cancers,[5] it is also clear that tumors of the same histological type show remarkably different clinical behavior. This is most evident in invasive ductal carcinomas of no special type (IDC-NST), where even tumors of the same histological grade may have distinct outcomes and dramatically different responses to systemic therapy.[2,3]

Using high-throughput technologies, particularly microarray analysis, several groups have proposed a new taxonomy for breast cancer based on their molecular features. The gene expression microarray-based class discovery studies pioneered by the Stanford group have led to the identification of at least five molecular breast cancer subtypes: luminal A, luminal B, normal breast-like, HER2, and basal-like.[6–11] Although based on the analysis of a limited number of samples and with somewhat different definitions for the various molecular groups in these studies, this approach to the classification of breast cancer has captured the attention of oncologists, pathologists, and scientists alike.

It should be noted, however, that this taxonomy has identified subgroups of breast cancer that were to some extent already known, and that the stability of the assignments of molecular subtypes by microarray-based methods has been called into question.[12–14] Indeed, the most robust distinction observed by microarray analysis is between the transcriptome of estrogen receptor-positive (ER+) and ER-negative (ER−) breast cancers.

Among the molecular subtypes of breast cancer identified through gene expression profiling studies, none has generated as much interest or controversy as the basal-like group. The purpose of this article was to review the current state of knowledge of basal-like breast cancers, to discuss the relationship between basal-like and triple-negative breast cancers, and to clarify practical implications of these diagnoses for pathologists and oncologists.

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