MicroRNAs as Molecular Biomarkers for the Characterization of Basal-like Breast Tumor Subtype

Abstract

Breast cancer is a heterogeneous disease highlighted by the presence of multiple tumor variants and the basal-like breast cancer (BLBC) is considered to be the most aggressive variant with limited therapeutics and a poor prognosis. Though the absence of detectable protein and hormonal receptors as biomarkers hinders early detection, the integration of genomic and transcriptomic profiling led to the identification of additional variants in BLBC. The high-throughput analysis of tissue-specific micro-ribonucleic acids (microRNAs/miRNAs) that are deemed to have a significant role in the development of breast cancer also displayed distinct expression profiles in each subtype of breast cancer and thus emerged to be a robust approach for the precise characterization of the BLBC subtypes. The classification schematic of breast cancer is still a fluid entity that continues to evolve alongside technological advancement, and the transcriptomic profiling of tissue-specific microRNAs is projected to aid in the substratification and diagnosis of the BLBC tumor subtype. In this review, we summarize the current knowledge on breast tumor classification, aim to collect comprehensive evidence based on the microRNA expression profiles, and explore their potential as prospective biomarkers of BLBC.

Keywords: basal-like breast cancer; classification; hormone receptors; microRNAs; transcriptomics; triple-negative breast cancer.

Figure 1

Evolution of breast cancer subclassification. Progression of breast cancer molecular subtyping schema [12,17,19,29,30,33,34]. Classification models are listed in chronological order from left to right. Blue lines denote correspondence to PAM50 luminal A subtype. Yellow lines denote correspondence to PAM50 luminal B subtype. Purple lines denote correspondence to PAM50 HER2-enriched subtype. Red lines denote correspondence to PAM50 basal-like subtype. Green lines denote correspondence to PAM50 normal-like subtype. _____ denotes correspondence to Herschkowitz et al.’s claudin-low subtype. - - - - encompasses studies completed by the Perou et al. group. ......... denotes classification model incorporating PAM50. [Abbreviations: ER—estrogen receptor; PR—progesterone receptor; HER2—human epidermal growth factor receptor 2; TNBC—triple-negative breast cancer; ErbB2—avian erythroblastic leukemia viral oncogene homolog 2; PAM50—prediction analysis of microarray 50].