Precision Medicine and Triple-Negative Breast Cancer: Current Landscape and Future Directions.

Fokhrul Hossain,Lucio Miele,Samarpan Majumder,Justin David

doi:10.3390/cancers13153739

Fokhrul Hossain, Lucio Miele + Show 2 more

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https://doi.org/10.3390/cancers13153739

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Abstract

Simple SummaryThe implementation of precision medicine will revolutionize cancer treatment paradigms. Notably, this goal is not far from reality: genetically similar cancers can be treated similarly. The heterogeneous nature of triple-negative breast cancer (TNBC) made it a suitable candidate to practice precision medicine. Using TNBC molecular subtyping and genomic profiling, a precision medicine-based clinical trial is ongoing. This review summarizes the current landscape and future directions of precision medicine and TNBC.Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer associated with a high recurrence and metastasis rate that affects African-American women disproportionately. The recent approval of targeted therapies for small subgroups of TNBC patients by the US ‘Food and Drug Administration’ is a promising development. The advancement of next-generation sequencing, particularly somatic exome panels, has raised hopes for more individualized treatment plans. However, the use of precision medicine for TNBC is a work in progress. This review will discuss the potential benefits and challenges of precision medicine for TNBC. A recent clinical trial designed to target TNBC patients based on their subtype-specific classification shows promise. Yet, tumor heterogeneity and sub-clonal evolution in primary and metastatic TNBC remain a challenge for oncologists to design adaptive precision medicine-based treatment plans.

Highlights

Cancers 2021, 13, 3739 developed based on genetic alterations was trastuzumab for cancers carrying genomic amplification of a region of chromosome 17 containing the ERBB2/HER2 gene, which led to better outcomes than first-line chemotherapy [16]
The rapid evolution of targeted therapy and immunotherapy guided by somatic and in some cases germline genomics gives us realistic hopes for the more effective, more precise, and less toxic treatment of Triple-negative breast cancer (TNBC) in the near future
Further research is necessary to realize the full potential of precision medicine in TNBC

Summary

Introduction

Cancers 2021, 13, 3739 developed based on genetic alterations was trastuzumab for cancers carrying genomic amplification of a region of chromosome 17 containing the ERBB2/HER2 gene, which led to better outcomes than first-line chemotherapy [16]. Increased adipose tissue caused by obesity increases the secretion of the hormone leptin, which enhances the expression of genes linked to stem cell-like properties and epithelial–mesenchymal transition [36] Another theory is that hyperinsulinemia secondary to insulin resistance increases the activation of the AKT/mTOR pathway, promoting proliferation and survival in TNBC cells. Liu et al classified TNBC tumors based on the expression profiles of both mRNAs and lncRNAs and proposed the Fudan University Shanghai Cancer Center (FUSCC) classification as well as the analysis of its interaction with the Lehman/Pietenpol subtypes [55] They divided TNBC tumors into four subtypes including the immunomodulatory subtype (IM), the mesenchymal-like subtype (MES), the luminal androgen receptor subtype (LAR), and the basal-like and immune-suppressed (BLIS) subtype [55].

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