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

Are Basal-like and Triple-negative Cancers Synonymous?

As should be evident from the foregoing discussion, although there are numerous similarities between basal-like and triple-negative breast cancers, these two terms are not synonymous, despite the fact that some have previously used these terms interchangeably.[10,15,53,68,69] It is true that the majority of triple-negative cancers are of basal-like phenotype[22,60,68] and the majority of tumors expressing 'basal' markers are triple-negative.[16,17,19,53,60,70] However, not all basal-like cancers determined by gene expression profiling lack ER, PR and HER2,[10,12,15,16,68,70–74] and conversely not all triple-negative cancers show a basal-like phenotype by expression array analysis. For example, Bertucci et al[70] showed that only 71% of triple-negative cancers were of basal-like subtype by gene expression profiling and that only 77% of molecular basal-like tumors were triple-negative. Similar results were observed by de Ronde et al[74] and Parker et al (Supplementary Table 1 of Parker et al[11]), where 8–29% of triple-negative cancers did not show a basal-like subtype by expression array analysis and 18–40% of basal-like breast cancers defined by gene expression profiling did not harbor a triple-negative phenotype. Further, there is a significant number of triple-negative cancers that do not express basal markers and are classified as normal breast-like (probably an artifact of gene expression profiling due to samples with disproportionately high content of stromal and normal breast epithelial cells),[11,75,76] molecular apocrine[77,78] (tumors with androgen receptor pathway activation, although a substantial proportion of these tumors may be classified as of HER2 subtype[78] using other molecular classification systems) or claudin-low[79,80] (cancers with transcriptomic features suggestive of epithelial to mesenchymal transition and reported to be enriched for the so-called 'cancer stem cells') subtype by gene expression profiling (for review, see Weigelt et al[12]). Apart from the more heterogeneous transcriptome, triple-negative cancers also show more varied histological features. Indeed, up to 10% of triple-negative tumors were reported to be of grade I in one study.[59] However, numerous other studies have failed to identify any grade I breast cancers with a triple-negative phenotype. Furthermore, other histological special types of breast cancer that do not show a basal-like phenotype by transcriptomic analysis have been shown to occasionally express a triple-negative phenotype, including apocrine carcinomas, pleomorphic lobular carcinomas, and some mixed duct-lobular cancers.[1,15,69] Taken together, these results are in accord with the concept that the triple-negative phenotype is not an ideal surrogate marker for basal-like breast cancers.[60,70,81]

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